Metabolic shift underlies recovery in reversible infantile respiratory chain deficiency

ABSTRACT: Reversible infantile respiratory chain deficiency (RIRCD) is a rare mitochondrial myopathy leading to severe metabolic disturbances in infants, which recover spontaneously after 6-months of age. RIRCD is associated with the homoplasmic m.14674T>C mitochondrial DNA mutation, however only ~1/100 carriers develop the disease. We studied 27 affected and 15 unaffected individuals from 19 families and found additional heterozygous mutations in nuclear genes interacting with mt-tRNAGlu including EARS2 and TRMU in the majority of affected individuals, but not in healthy carriers of m.14674T>C, supporting a digenic inheritance. Our transcriptomics and proteomics analysis of patient muscle suggests a stepwise mechanism where first, the integrated stress-response associated with increased FGF21

SUBMITTER: Denisa Hathazi 

PROVIDER: S-SCDT-EMBOJ-2020-105364-T | biostudies-other |

REPOSITORIES: biostudies-other