Human diseases associated with defects in assembly of OXPHOS complexes
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Authors
Zeviani, Massimo
Publication Date
2018-07-20Journal Title
Essays in Biochemistry
ISSN
0071-1365
Publisher
Portland Press
Volume
62
Issue
3
Pages
271-286
Type
Article
Metadata
Show full item recordCitation
Zeviani, M. (2018). Human diseases associated with defects in assembly of OXPHOS complexes. Essays in Biochemistry, 62 (3), 271-286. https://doi.org/10.1042/EBC20170099
Abstract
The structural biogenesis and functional proficiency of the multiheteromeric complexes forming the mitochondrial oxidative phosphorylation system 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 has led and will allow to identify additional components of the assembly machinery of individual complexes, mutations of which are responsible for human disorders. The functional studies on patients’ specimen, together with the creation and characterization of in vivo 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 actors 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, III and IV.
Sponsorship
MRC (MC_UP_1002/1)
Medical Research Council (MC_UU_00015/8)
MRC (MC_UU_00015/8)
Identifiers
External DOI: https://doi.org/10.1042/EBC20170099
This record's URL: https://www.repository.cam.ac.uk/handle/1810/282843
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