In:
Journal of Cell Science, The Company of Biologists
Abstract:
Prohibitins (prohibitin 1, PHB1, and prohibitin 2, PHB2) are evolutionally conserved and ubiquitously expressed mitochondrial protein. PHBs form multimeric ring complexes acting as scaffolds in the inner mitochondrial membrane. Mitochondrial flashes (mitoflashes) are newly discovered mitochondrial signaling events which reflect electrical and chemical excitations of the organelle. Here we investigate possible roles of PHBs in the regulation of mitoflash signaling. Down-regulation of PHBs increases mitoflash frequency by up to 5.4 folds due to elevated basal reactive oxygen species (ROS) production of the mitochondria. Mechanistically, PHB deficiency impairs the formation of mitochondrial respiratory supercomplexes (RSCs) without altering the abundance of individual respiratory complex subunits. These impairments induced by PHB deficiency are effectively rescued by co-expression of PHB1 and PHB2, indicating that the multimeric PHB complex acts as the functional unit. Furthermore, down-regulating other RSC assembly factors, including SCAFI, RCF1a, RCF1b, UQCC3, and SLP2, all activate mitoflashes through elevating mitochondrial ROS production. Our findings identify PHB complex as a new regulator of RSC formation and mitoflash signaling, and delineate a general relationship among RSC formation, basal ROS production, and mitoflash biogenesis.
Type of Medium:
Online Resource
ISSN:
1477-9137
,
0021-9533
Language:
English
Publisher:
The Company of Biologists
Publication Date:
2017
detail.hit.zdb_id:
219171-4
detail.hit.zdb_id:
1483099-1
SSG:
12
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