* 607381

TRANSLOCASE OF INNER MITOCHONDRIAL MEMBRANE 50; TIMM50


Alternative titles; symbols

TRANSLOCASE OF INNER MITOCHONDRIAL MEMBRANE 50, YEAST, HOMOLOG OF; TIM50


HGNC Approved Gene Symbol: TIMM50

Cytogenetic location: 19q13.2     Genomic coordinates (GRCh38): 19:39,480,838-39,493,779 (from NCBI)


Gene-Phenotype Relationships
Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
19q13.2 3-methylglutaconic aciduria, type IX 617698 AR 3

TEXT

Description

The TIMM50 gene encodes a subunit of the mitochondrial presequence import machinery called the TIM23 complex. TIMM50 serves as a major receptor in the intermembrane space that binds to proteins on their way to cross the mitochondrial inner membrane (summary by Shahrour et al., 2017).


Cloning and Expression

Yamamoto et al. (2002) identified Tim50, a component of the yeast Tim23 (605034) import machinery, which mediates translocation of presequence-containing proteins across the mitochondrial inner membrane. By searching sequence databases, they identified open reading frames encoding proteins with similarity to Tim50 and with a putative mitochondrial presequence in the genomes of evolutionarily distant organisms, including human.


Gene Function

Yamamoto et al. (2002) determined that yeast Tim50 is anchored to the inner mitochondrial membrane, exposing the C-terminal domain to the intermembrane space. Tim50 was found to interact with the N-terminal intermembrane space domain of Tim23. Functional defects of Tim50 either by depletion of the protein or addition of anti-Tim50 antibodies blocked the protein translocation across the inner membrane. A translocation intermediate accumulated at the translocator of the outer mitochondrial membrane (TOM) complex was cross-linked to Tim50. The authors concluded that Tim50, in cooperation with Tim23, facilitates transfer of the translocating protein from the TOM complex to the Tim23 complex.

Meinecke et al. (2006) found that the intermembrane space domain of Tim50 induced the Tim23 channel to close. Presequences overcame this effect and activated the channel for translocation. Thus, Meinecke et al. (2006) concluded that the hydrophilic cis domain of Tim50 maintains the permeability barrier of mitochondria by closing the translocation pore in a presequence-regulated manner.


Mapping

Gross (2014) mapped the TIMM50 gene to chromosome 19q13.2 based on an alignment of the TIMM50 sequence (GenBank AY444561) with the genomic sequence (GRCh37).


Molecular Genetics

In 4 patients from 2 unrelated consanguineous families with 3-methylglutaconic aciduria type IX (MGCA9; 617698), Shahrour et al. (2017) identified homozygous missense mutations in the TIMM50 gene (T252M, 607381.0001 and R217W, 607381.0002). The mutations, which were found by exome sequencing, segregated with the disorder in the family. The human homolog of TIMM50 failed to rescue a Tim50-null growth defect in yeast, and expression of the homologous substitution for R217W (R159W) in yeast resulted in normal growth and did not impair the import function of Tim50. These findings indicated that this substitution is tolerated in yeast, but not in humans. Although Shahrour et al. (2017) could not demonstrate the pathogenicity of the mutations in a yeast-based system, they concluded that they are disease-causing.

By whole-exome sequencing in a 20-month-old girl, born to consanguineous Saudi parents, with MGCA9, Mir et al. (2020) identified homozygosity for the T252M mutation in the TIMM50 gene.

In a child with MGCA9, Reyes et al. (2018) identified compound heterozygous mutations in the TIMM50 gene (S112X, 607381.0003 and G190A, 607381.0004). The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. Each parent was heterozygous for one of the mutations. Patient fibroblasts had reduced mitochondrial membrane potential, impaired TIM23-dependent protein import, and reduced steady state levels of tested subunits of respiratory chain complexes I, II, and IV. Introduction of wildtype TIMM50 into patient fibroblasts remediated these defects. When patient fibroblasts were grown in galactose-containing media (which is dependent on oxidative phosphorylation) compared to glucose containing media (which is reliant on glycolytic metabolism), improvement in expression of members of the TIM23 transport complex, levels of subunits of respiratory chain complexes, and ATP-dependent respiration was seen, although apoptosis was increased.

In a 17-year-old boy with MGCA9, Tort et al. (2019) identified compound heterozygous mutations in the TIMM50 gene (R114Q, 607381.0005; G269S, 607381.0006). Testing in patient fibroblasts demonstrated normal TIMM50 mRNA levels and reduced protein levels, indicating that the mutations may affect protein stability. In patient fibroblasts, expression of 10 subunits of the mitochondrial respiratory chain and localization of 6 subunits of the respiratory chain in the mitochondrial inner membrane were normal, indicating that the TIMM50 mutations did not disrupt mitochondrial protein expression or localization. Microscopy in patient fibroblasts showed abnormal mitochondrial cristae structure. BN-PAGE analysis in patient fibroblasts showed reduced mitochondrial respiratory chain complexes I, II, IV, and V and reduced levels of respiratory supercomplexes, and respirometry demonstrated decreased maximal respiratory capacity. The studies indicated a role for TIMM50 in cristae maintenance and assembly of OXPHOS complexes and supercomplexes.


ALLELIC VARIANTS ( 6 Selected Examples):

.0001 3-@METHYLGLUTACONIC ACIDURIA, TYPE IX

TIMM50, THR252MET
  
RCV000509024

In 2 sibs, born of consanguineous Bedouin parents (family A), with 3-methylglutaconic aciduria type IX (MGCA9; 617698), Shahrour et al. (2017) identified a homozygous c.755C-T transition (c.755C-T, NM_001001563.1) in the TIMM50 gene, resulting in a thr252-to-met (T252M) substitution at a highly conserved residue in the mitochondrial intermembrane space. The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing, segregated with the disorder in the family. A fetus was also found to be homozygous for the mutation. The mutation was not present in large cohorts of control exome analyses or in an ethnic-specific exome cohort. Functional studies of the variant were not performed.

By whole-exome sequencing in a 20-month-old girl, born to consanguineous Saudi parents, with MGCA9, Mir et al. (2020) identified homozygosity for the T252M mutation in the TIMM50 gene.


.0002 3-@METHYLGLUTACONIC ACIDURIA, TYPE IX

TIMM50, ARG217TRP
  
RCV000509033...

In 2 sibs, born of consanguineous Muslim parents (family B), with 3-methylglutaconic aciduria type IX (MGCA9; 617698), Shahrour et al. (2017) identified a homozygous c.649C-T transition (c.649C-T, NM_001001563.1) in the TIMM50 gene, resulting in an arg217-to-trp (R217W) substitution at a conserved residue in the mitochondrial intermembrane space. The mutation, which was found by exome sequencing, segregated with the disorder in the family. It was not found in the ExAC database or in 700 in-house control exomes.


.0003 3-@METHYLGLUTACONIC ACIDURIA, TYPE IX

TIMM50, SER112TER
  
RCV000677434...

In an Italian child with 3-methylglutaconic aciduria type IX (MGCA9; 617698), Reyes et al. (2018) identified compound heterozygous mutations in the TIMM50 gene: a c.335C-A transversion (c.335C-A, NM_001001563) in exon 1, resulting in a ser112-to-ter (S112X) substitution, and a c.569G-C transversion in exon 3, resulting in a gly190-to-ala (G190A; 607381.0004) substitution. The mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. The parents were shown to be carriers. The S112X mutation was not present in the ExAC database, and the G190A mutation was present in ExAC in only 1 of approximately 200,000 alleles. TIMM50 protein expression, as well as protein expression of other members of the mitochondrial TIM23 transport complex, was reduced in patient fibroblasts. Import of TFAM (600438) into mitochondria via the TIM23 complex was severely impaired in patient fibroblasts.


.0004 3-@METHYLGLUTACONIC ACIDURIA, TYPE IX

TIMM50, GLY190ALA (rs776019250)
  
RCV000677433...

For discussion of the c.569G-C transversion (c.569G-C, NM_001001563) in the TIMM50 gene, resulting in a gly190-to-ala (G190A) substitution, that was found in compound heterozygous state in a patient with 3-methylglutaconic aciduria type IX (MGCA9; 617698), by Reyes et al. (2018), see 607381.0003.


.0005 3-@METHYLGLUTACONIC ACIDURIA, TYPE IX

TIMM50, ARG114GLN
  
RCV001812628...

In a 17-year-old patient with 3-methylglutaconic aciduria type IX (MGCA9; 617698), Tort et al. (2019) identified compound heterozygous mutations in the TIMM50 gene: a c.341G-A transition (c.341G-A, NM_001001563.5), resulting in an arg114-to-gln (R114Q) substitution, inherited from the mother, and a c.805G-A transition, resulting in a gly269-to-ser (G269S; 607381.0006) substitution, inherited from the father. Both mutations occurred at highly conserved residues. The mutations were identified by trio exome sequencing and confirmed by Sanger sequencing. Testing in patient fibroblasts demonstrated normal TIMM50 mRNA levels and reduced protein levels, indicating that the mutations may affect protein stability. Microscopy in patient fibroblasts showed abnormal mitochondrial cristae structure. BN-PAGE analysis in patient fibroblasts showed reduced mitochondrial respiratory chain complexes I, II, IV, and V and reduced levels of respiratory supercomplexes.


.0006 3-@METHYLGLUTACONIC ACIDURIA, TYPE IX

TIMM50, GLY269SER
  
RCV000190713...

For discussion of the c.805G-A transition (c.805G-A, NM_001001563.5) in the TIMM50 gene, resulting in a gly269-to-ser (G269S) substitution, that was found in compound heterozygous state in a patient with 3-methylglutaconic aciduria type IX (MGCA9; 617698) by Tort et al. (2019), see 607381.0005.


REFERENCES

  1. Gross, M. B. Personal Communication. Baltimore, Md. 5/29/2014.

  2. Meinecke, M., Wagner, R., Kovermann, P., Guiard, B., Mick, D. U., Hutu, D. P., Voos, W., Truscott, K. N., Chacinska, A., Pfanner, N., Rehling, P. Tim50 maintains the permeability barrier of the mitochondrial inner membrane. Science 312: 1523-1526, 2006. [PubMed: 16763150, related citations] [Full Text]

  3. Mir, A., Hadab, S., Sammak, M., Alhazmi, R., Housawi, Y., Bashir, S. Complete resolution of epileptic spasms with vigabatrin in a patient with 3-methylglutaconic aciduria caused by TIMM50 gene mutation. (Letter) Clin. Genet. 98: 102-103, 2020. [PubMed: 32369862, related citations] [Full Text]

  4. Reyes, A., Melchionda, L., Burlina, A., Robinson, A. J., Ghezzi, D., Zeviani, M. Mutations in TIMM50 compromise cell survival in OxPhos-dependent metabolic conditions. EMBO Molec. Med. 10: e8698, 2018. Note: Electronic Article. [PubMed: 30190335, images, related citations] [Full Text]

  5. Shahrour, M. A., Staretz-Chacham , O., Dayan, D., Stephen, J., Weech, A., Damseh, N., Pri Chen, H., Edvardson, S., Mazaheri, S., Saada, A., NISC Intramural Sequencing, Hershkovitz, E., and 9 others. Mitochondrial epileptic encephalopathy, 3-methylglutaconic aciduria and variable complex V deficiency associated with TIMM50 mutations. Clin. Genet. 91: 690-696, 2017. [PubMed: 27573165, images, related citations] [Full Text]

  6. Tort, F., Ugarteburu, O., Texido, L., Gea-Sorli, S., Garcia-Villoria, J., Ferrer-Cortes, X., Arias, A., Matalonga, L., Gort, L., Ferrer, I., Guitart-Mampel, M., Garrabou, G., and 9 others. Mutations in TIMM50 cause severe mitochondrial dysfunction by targeting key aspects of mitochondrial physiology. Hum. Mutat. 40: 1700-1712, 2019. [PubMed: 31058414, related citations] [Full Text]

  7. Yamamoto, H., Esaki, M., Kanamori, T., Tamura, Y., Nishikawa, S., Endo, T. Tim50 is a subunit of the TIM23 complex that links protein translocation across the outer and inner mitochondrial membranes. Cell 111: 519-528, 2002. [PubMed: 12437925, related citations] [Full Text]


Hilary J. Vernon - updated : 01/14/2022
Hilary J. Vernon - updated : 03/15/2021
Hilary J. Vernon - updated : 02/01/2021
Cassandra L. Kniffin - updated : 10/03/2017
Matthew B. Gross - updated : 05/29/2014
Ada Hamosh - updated : 7/24/2006
Creation Date:
Stylianos E. Antonarakis : 11/25/2002
carol : 01/14/2022
carol : 03/16/2021
carol : 03/15/2021
carol : 02/11/2021
carol : 02/01/2021
mgross : 05/04/2020
carol : 12/18/2019
alopez : 10/03/2017
ckniffin : 10/03/2017
mgross : 05/29/2014
terry : 7/24/2006
alopez : 12/1/2004
mgross : 11/25/2002

* 607381

TRANSLOCASE OF INNER MITOCHONDRIAL MEMBRANE 50; TIMM50


Alternative titles; symbols

TRANSLOCASE OF INNER MITOCHONDRIAL MEMBRANE 50, YEAST, HOMOLOG OF; TIM50


HGNC Approved Gene Symbol: TIMM50

SNOMEDCT: 1222672002;  


Cytogenetic location: 19q13.2     Genomic coordinates (GRCh38): 19:39,480,838-39,493,779 (from NCBI)


Gene-Phenotype Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
19q13.2 3-methylglutaconic aciduria, type IX 617698 Autosomal recessive 3

TEXT

Description

The TIMM50 gene encodes a subunit of the mitochondrial presequence import machinery called the TIM23 complex. TIMM50 serves as a major receptor in the intermembrane space that binds to proteins on their way to cross the mitochondrial inner membrane (summary by Shahrour et al., 2017).


Cloning and Expression

Yamamoto et al. (2002) identified Tim50, a component of the yeast Tim23 (605034) import machinery, which mediates translocation of presequence-containing proteins across the mitochondrial inner membrane. By searching sequence databases, they identified open reading frames encoding proteins with similarity to Tim50 and with a putative mitochondrial presequence in the genomes of evolutionarily distant organisms, including human.


Gene Function

Yamamoto et al. (2002) determined that yeast Tim50 is anchored to the inner mitochondrial membrane, exposing the C-terminal domain to the intermembrane space. Tim50 was found to interact with the N-terminal intermembrane space domain of Tim23. Functional defects of Tim50 either by depletion of the protein or addition of anti-Tim50 antibodies blocked the protein translocation across the inner membrane. A translocation intermediate accumulated at the translocator of the outer mitochondrial membrane (TOM) complex was cross-linked to Tim50. The authors concluded that Tim50, in cooperation with Tim23, facilitates transfer of the translocating protein from the TOM complex to the Tim23 complex.

Meinecke et al. (2006) found that the intermembrane space domain of Tim50 induced the Tim23 channel to close. Presequences overcame this effect and activated the channel for translocation. Thus, Meinecke et al. (2006) concluded that the hydrophilic cis domain of Tim50 maintains the permeability barrier of mitochondria by closing the translocation pore in a presequence-regulated manner.


Mapping

Gross (2014) mapped the TIMM50 gene to chromosome 19q13.2 based on an alignment of the TIMM50 sequence (GenBank AY444561) with the genomic sequence (GRCh37).


Molecular Genetics

In 4 patients from 2 unrelated consanguineous families with 3-methylglutaconic aciduria type IX (MGCA9; 617698), Shahrour et al. (2017) identified homozygous missense mutations in the TIMM50 gene (T252M, 607381.0001 and R217W, 607381.0002). The mutations, which were found by exome sequencing, segregated with the disorder in the family. The human homolog of TIMM50 failed to rescue a Tim50-null growth defect in yeast, and expression of the homologous substitution for R217W (R159W) in yeast resulted in normal growth and did not impair the import function of Tim50. These findings indicated that this substitution is tolerated in yeast, but not in humans. Although Shahrour et al. (2017) could not demonstrate the pathogenicity of the mutations in a yeast-based system, they concluded that they are disease-causing.

By whole-exome sequencing in a 20-month-old girl, born to consanguineous Saudi parents, with MGCA9, Mir et al. (2020) identified homozygosity for the T252M mutation in the TIMM50 gene.

In a child with MGCA9, Reyes et al. (2018) identified compound heterozygous mutations in the TIMM50 gene (S112X, 607381.0003 and G190A, 607381.0004). The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. Each parent was heterozygous for one of the mutations. Patient fibroblasts had reduced mitochondrial membrane potential, impaired TIM23-dependent protein import, and reduced steady state levels of tested subunits of respiratory chain complexes I, II, and IV. Introduction of wildtype TIMM50 into patient fibroblasts remediated these defects. When patient fibroblasts were grown in galactose-containing media (which is dependent on oxidative phosphorylation) compared to glucose containing media (which is reliant on glycolytic metabolism), improvement in expression of members of the TIM23 transport complex, levels of subunits of respiratory chain complexes, and ATP-dependent respiration was seen, although apoptosis was increased.

In a 17-year-old boy with MGCA9, Tort et al. (2019) identified compound heterozygous mutations in the TIMM50 gene (R114Q, 607381.0005; G269S, 607381.0006). Testing in patient fibroblasts demonstrated normal TIMM50 mRNA levels and reduced protein levels, indicating that the mutations may affect protein stability. In patient fibroblasts, expression of 10 subunits of the mitochondrial respiratory chain and localization of 6 subunits of the respiratory chain in the mitochondrial inner membrane were normal, indicating that the TIMM50 mutations did not disrupt mitochondrial protein expression or localization. Microscopy in patient fibroblasts showed abnormal mitochondrial cristae structure. BN-PAGE analysis in patient fibroblasts showed reduced mitochondrial respiratory chain complexes I, II, IV, and V and reduced levels of respiratory supercomplexes, and respirometry demonstrated decreased maximal respiratory capacity. The studies indicated a role for TIMM50 in cristae maintenance and assembly of OXPHOS complexes and supercomplexes.


ALLELIC VARIANTS 6 Selected Examples):

.0001   3-@METHYLGLUTACONIC ACIDURIA, TYPE IX

TIMM50, THR252MET
SNP: rs1244226820, gnomAD: rs1244226820, ClinVar: RCV000509024

In 2 sibs, born of consanguineous Bedouin parents (family A), with 3-methylglutaconic aciduria type IX (MGCA9; 617698), Shahrour et al. (2017) identified a homozygous c.755C-T transition (c.755C-T, NM_001001563.1) in the TIMM50 gene, resulting in a thr252-to-met (T252M) substitution at a highly conserved residue in the mitochondrial intermembrane space. The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing, segregated with the disorder in the family. A fetus was also found to be homozygous for the mutation. The mutation was not present in large cohorts of control exome analyses or in an ethnic-specific exome cohort. Functional studies of the variant were not performed.

By whole-exome sequencing in a 20-month-old girl, born to consanguineous Saudi parents, with MGCA9, Mir et al. (2020) identified homozygosity for the T252M mutation in the TIMM50 gene.


.0002   3-@METHYLGLUTACONIC ACIDURIA, TYPE IX

TIMM50, ARG217TRP
SNP: rs1300848445, gnomAD: rs1300848445, ClinVar: RCV000509033, RCV001367110

In 2 sibs, born of consanguineous Muslim parents (family B), with 3-methylglutaconic aciduria type IX (MGCA9; 617698), Shahrour et al. (2017) identified a homozygous c.649C-T transition (c.649C-T, NM_001001563.1) in the TIMM50 gene, resulting in an arg217-to-trp (R217W) substitution at a conserved residue in the mitochondrial intermembrane space. The mutation, which was found by exome sequencing, segregated with the disorder in the family. It was not found in the ExAC database or in 700 in-house control exomes.


.0003   3-@METHYLGLUTACONIC ACIDURIA, TYPE IX

TIMM50, SER112TER
SNP: rs35135520, gnomAD: rs35135520, ClinVar: RCV000677434, RCV001328000

In an Italian child with 3-methylglutaconic aciduria type IX (MGCA9; 617698), Reyes et al. (2018) identified compound heterozygous mutations in the TIMM50 gene: a c.335C-A transversion (c.335C-A, NM_001001563) in exon 1, resulting in a ser112-to-ter (S112X) substitution, and a c.569G-C transversion in exon 3, resulting in a gly190-to-ala (G190A; 607381.0004) substitution. The mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. The parents were shown to be carriers. The S112X mutation was not present in the ExAC database, and the G190A mutation was present in ExAC in only 1 of approximately 200,000 alleles. TIMM50 protein expression, as well as protein expression of other members of the mitochondrial TIM23 transport complex, was reduced in patient fibroblasts. Import of TFAM (600438) into mitochondria via the TIM23 complex was severely impaired in patient fibroblasts.


.0004   3-@METHYLGLUTACONIC ACIDURIA, TYPE IX

TIMM50, GLY190ALA ({dbSNP rs776019250})
SNP: rs776019250, gnomAD: rs776019250, ClinVar: RCV000677433, RCV001328001

For discussion of the c.569G-C transversion (c.569G-C, NM_001001563) in the TIMM50 gene, resulting in a gly190-to-ala (G190A) substitution, that was found in compound heterozygous state in a patient with 3-methylglutaconic aciduria type IX (MGCA9; 617698), by Reyes et al. (2018), see 607381.0003.


.0005   3-@METHYLGLUTACONIC ACIDURIA, TYPE IX

TIMM50, ARG114GLN
SNP: rs778355943, gnomAD: rs778355943, ClinVar: RCV001812628, RCV003120700

In a 17-year-old patient with 3-methylglutaconic aciduria type IX (MGCA9; 617698), Tort et al. (2019) identified compound heterozygous mutations in the TIMM50 gene: a c.341G-A transition (c.341G-A, NM_001001563.5), resulting in an arg114-to-gln (R114Q) substitution, inherited from the mother, and a c.805G-A transition, resulting in a gly269-to-ser (G269S; 607381.0006) substitution, inherited from the father. Both mutations occurred at highly conserved residues. The mutations were identified by trio exome sequencing and confirmed by Sanger sequencing. Testing in patient fibroblasts demonstrated normal TIMM50 mRNA levels and reduced protein levels, indicating that the mutations may affect protein stability. Microscopy in patient fibroblasts showed abnormal mitochondrial cristae structure. BN-PAGE analysis in patient fibroblasts showed reduced mitochondrial respiratory chain complexes I, II, IV, and V and reduced levels of respiratory supercomplexes.


.0006   3-@METHYLGLUTACONIC ACIDURIA, TYPE IX

TIMM50, GLY269SER
SNP: rs797044891, ClinVar: RCV000190713, RCV001812182

For discussion of the c.805G-A transition (c.805G-A, NM_001001563.5) in the TIMM50 gene, resulting in a gly269-to-ser (G269S) substitution, that was found in compound heterozygous state in a patient with 3-methylglutaconic aciduria type IX (MGCA9; 617698) by Tort et al. (2019), see 607381.0005.


REFERENCES

  1. Gross, M. B. Personal Communication. Baltimore, Md. 5/29/2014.

  2. Meinecke, M., Wagner, R., Kovermann, P., Guiard, B., Mick, D. U., Hutu, D. P., Voos, W., Truscott, K. N., Chacinska, A., Pfanner, N., Rehling, P. Tim50 maintains the permeability barrier of the mitochondrial inner membrane. Science 312: 1523-1526, 2006. [PubMed: 16763150] [Full Text: https://doi.org/10.1126/science.1127628]

  3. Mir, A., Hadab, S., Sammak, M., Alhazmi, R., Housawi, Y., Bashir, S. Complete resolution of epileptic spasms with vigabatrin in a patient with 3-methylglutaconic aciduria caused by TIMM50 gene mutation. (Letter) Clin. Genet. 98: 102-103, 2020. [PubMed: 32369862] [Full Text: https://doi.org/10.1111/cge.13763]

  4. Reyes, A., Melchionda, L., Burlina, A., Robinson, A. J., Ghezzi, D., Zeviani, M. Mutations in TIMM50 compromise cell survival in OxPhos-dependent metabolic conditions. EMBO Molec. Med. 10: e8698, 2018. Note: Electronic Article. [PubMed: 30190335] [Full Text: https://doi.org/10.15252/emmm.201708698]

  5. Shahrour, M. A., Staretz-Chacham , O., Dayan, D., Stephen, J., Weech, A., Damseh, N., Pri Chen, H., Edvardson, S., Mazaheri, S., Saada, A., NISC Intramural Sequencing, Hershkovitz, E., and 9 others. Mitochondrial epileptic encephalopathy, 3-methylglutaconic aciduria and variable complex V deficiency associated with TIMM50 mutations. Clin. Genet. 91: 690-696, 2017. [PubMed: 27573165] [Full Text: https://doi.org/10.1111/cge.12855]

  6. Tort, F., Ugarteburu, O., Texido, L., Gea-Sorli, S., Garcia-Villoria, J., Ferrer-Cortes, X., Arias, A., Matalonga, L., Gort, L., Ferrer, I., Guitart-Mampel, M., Garrabou, G., and 9 others. Mutations in TIMM50 cause severe mitochondrial dysfunction by targeting key aspects of mitochondrial physiology. Hum. Mutat. 40: 1700-1712, 2019. [PubMed: 31058414] [Full Text: https://doi.org/10.1002/humu.23779]

  7. Yamamoto, H., Esaki, M., Kanamori, T., Tamura, Y., Nishikawa, S., Endo, T. Tim50 is a subunit of the TIM23 complex that links protein translocation across the outer and inner mitochondrial membranes. Cell 111: 519-528, 2002. [PubMed: 12437925] [Full Text: https://doi.org/10.1016/s0092-8674(02)01053-x]


Contributors:
Hilary J. Vernon - updated : 01/14/2022
Hilary J. Vernon - updated : 03/15/2021
Hilary J. Vernon - updated : 02/01/2021
Cassandra L. Kniffin - updated : 10/03/2017
Matthew B. Gross - updated : 05/29/2014
Ada Hamosh - updated : 7/24/2006

Creation Date:
Stylianos E. Antonarakis : 11/25/2002

Edit History:
carol : 01/14/2022
carol : 03/16/2021
carol : 03/15/2021
carol : 02/11/2021
carol : 02/01/2021
mgross : 05/04/2020
carol : 12/18/2019
alopez : 10/03/2017
ckniffin : 10/03/2017
mgross : 05/29/2014
terry : 7/24/2006
alopez : 12/1/2004
mgross : 11/25/2002