Open AccessDeficiency of PHB complex impairs respiratory supercomplex formation and activates mitochondrial flashes
Author(s) -
Chongshu Jian,
Fengli Xu,
Tingting Hou,
Tao Sun,
Jinghang Li,
Heping Cheng,
Xianhua Wang
Publication year - 2017
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.198523
Subject(s) - prohibitin , biology , chromatin structure remodeling (rsc) complex , microbiology and biotechnology , biogenesis , mitochondrion , reactive oxygen species , mitochondrial ros , biochemistry , dna , histone , nucleosome , gene
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.