Oxidative Phosphorylation Diseases

Abstract

Oxidative phosphorylation (OXPHOS) is composed of five intramitochondrial enzyme complexes (complexes I to V) that are responsible for producing the majority of the ATP required for normal cellular function. Assembly and maintenance of OXPHOS requires the coordinate regulation of nuclear DNA and mitochondrial DNA (mtDNA) genes. The mtDNA encodes 12 OXPHOS subunits, 22 tRNAs, and 2 rRNAs, which provide the core elements for OXPHOS function and mitochondrial protein synthesis. The nuclear DNA is responsible for synthesizing approximately 70 OXPHOS subunits, transporting them to the mitochondria via chaperone proteins, ensuring their passage across the mitochondrial inner membrane, and coordinating their proper processing and assembly. OXPHOS is regulated by a wide variety of factors and processes that include hormone levels, oxygen supply, ion gradients, membrane transporters such as the adenine nucleotide translocase that supplies ADP for conversion to ATP, transcription factors that alter the levels of nuclear gene transcription, tissue-specific isoforms, developmental-specific isoforms, mitochondrial replication, mitochondrial transcription, and mitochondrial translation. Defects in any of these processes may produce an OXPHOS disease.