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Reyes 2018 EMBO Mol Med
Additional label Labels  + , 2018-11  +
Coupling states LEAK  + , ET  +
Enzyme Inner mt-membrane transporter  +
Has abstract TIMM50 is an essential component of the TI
TIMM50 is an essential component of the TIM23 complex, the mitochondrial inner membrane machinery that imports cytosolic proteins containing a mitochondrial targeting presequence into the mitochondrial inner compartment. Whole exome sequencing (WES) identified compound heterozygous pathogenic mutations in TIMM50 in an infant patient with rapidly progressive, severe encephalopathy. Patient fibroblasts presented low levels of TIMM50 and other components of the TIM23 complex, lower mitochondrial membrane potential, and impaired TIM23-dependent protein import. As a consequence, steady-state levels of several components of mitochondrial respiratory chain were decreased, resulting in decreased respiration and increased ROS production. Growth of patient fibroblasts in galactose shifted energy production metabolism toward oxidative phosphorylation (OxPhos), producing an apparent improvement in most of the above features but also increased apoptosis. Complementation of patient fibroblasts with TIMM50 improved or restored these features to control levels. Moreover, ''RNASEH1'' and ''ISCU'' mutant fibroblasts only shared a few of these features with ''TIMM50'' mutant fibroblasts. Our results indicate that mutations in ''TIMM50'' cause multiple mitochondrial bioenergetic dysfunction and that functional TIMM50 is essential for cell survival in OxPhos-dependent conditions.
l survival in OxPhos-dependent conditions.  +
Has editor [[Plangger M]]  +
Has info [https://www.ncbi.nlm.nih.gov/pubmed/30190335 PMID: 30190335 Open Access]  +
Has publicationkeywords OxPhos  + , TIMM50  + , Bioenergetic dysfunction  + , Mitochondrial import  +
Has title Reyes A, Melchionda L, Burlina A, Robinson AJ, Ghezzi D, Zeviani M (2018) Mutations in TIMM50 compromise cell survival in OxPhos-dependent metabolic conditions. EMBO Mol Med 10:e8698.  +
Instrument and method Oxygraph-2k  +
Mammal and model Human  +
MiP area Respiration  + , nDNA;cell genetics  +
Pathways ROX  +
Preparation Intact cells  +
Tissue and cell Fibroblast  +
Was published in journal EMBO Mol Med +
Was published in year 2018  +
Was written by Reyes A + , Melchionda L + , Burlina A + , Robinson AJ + , Ghezzi D + , Zeviani M +
Categories Publications
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
13:01:55, 12 November 2018  +
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