Abstract：
:The biogenesis and function of the mitochondrial respiratory chain (RC) involve the organization of RC enzyme complexes in supercomplexes or respirasomes through an unknown biosynthetic process. This leads to structural interdependences between RC complexes, which are highly relevant from biological and biomedical perspectives, because RC defects often lead to severe neuromuscular disorders. We show that in human cells, respirasome biogenesis involves a complex I assembly intermediate acting as a scaffold for the combined incorporation of complexes III and IV subunits, rather than originating from the association of preassembled individual holoenzymes. The process ends with the incorporation of complex I NADH dehydrogenase catalytic module, which leads to the respirasome activation. While complexes III and IV assemble either as free holoenzymes or by incorporation of free subunits into supercomplexes, the respirasomes constitute the structural units where complex I is assembled and activated, thus explaining the significance of the respirasomes for RC function.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Moreno-Lastres D,Fontanesi F,García-Consuegra I,Martín MA,Arenas J,Barrientos A,Ugalde Cdoi
10.1016/j.cmet.2012.01.015subject
Has Abstractpub_date
2012-03-07 00:00:00pages
324-35issue
3eissn
1550-4131issn
1932-7420pii
S1550-4131(12)00022-8journal_volume
15pub_type
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