Human diseases associated with defects in assembly of OXPHOS complexes.

TitleHuman diseases associated with defects in assembly of OXPHOS complexes.
Publication TypeJournal Article
Year of Publication2018
AuthorsGhezzi, D, Zeviani, M
JournalEssays Biochem
Date Published2018 07 20
KeywordsHumans, Mitochondrial Diseases, Multienzyme Complexes, Mutation, Oxidative Phosphorylation

The structural biogenesis and functional proficiency of the multiheteromeric complexes forming the mitochondrial oxidative phosphorylation system (OXPHOS) require the concerted action of a number of chaperones and other assembly factors, most of which are specific for each complex. Mutations in a large number of these assembly factors are responsible for mitochondrial disorders, in most cases of infantile onset, typically characterized by biochemical defects of single specific complexes. In fact, pathogenic mutations in complex-specific assembly factors outnumber, in many cases, the repertoire of mutations found in structural subunits of specific complexes. The identification of patients with specific defects in assembly factors has provided an important contribution to the nosological characterization of mitochondrial disorders, and has also been a crucial means to identify a huge number of these proteins in humans, which play an essential role in mitochondrial bioenergetics. The wide use of next generation sequencing (NGS) has led to and will allow the identifcation of additional components of the assembly machinery of individual complexes, mutations of which are responsible for human disorders. The functional studies on patients' specimens, together with the creation and characterization of models, are fundamental to better understand the mechanisms of each of them. A new chapter in this field will be, in the near future, the discovery of mechanisms and actions underlying the formation of supercomplexes, molecular structures formed by the physical, and possibly functional, interaction of some of the individual respiratory complexes, particularly complex I (CI), III (CIII), and IV (CIV).

Alternate JournalEssays Biochem.
Citation Key10.1042/EBC20170099
PubMed ID30030362
PubMed Central IDPMC6056716