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ETFDH, CIII and COQ2 common interactome

ABSTRACT: Proteomic analysis of the immunocapture (IP) of COQ2, ETFDH and UQCRC2 in skeletal muscle extracts, searching for common interactors Coenzyme Q (Q) is a key lipid electron transporter, but several aspects of its biosynthesis and redox homeostasis remain undefined. Various flavoproteins reduce the Q; however, in eukaryotes, only the OXPHOS-complex III (CIII) oxidizes the QH2. The mechanism of action of CIII is still debated. We demonstrate that the Q-reductase ETFDH is essential for CIII activity in skeletal muscle. We identify a complex involving ETFDH, CIII, and the Q-biosynthesis regulator COQ2 that directs electrons from lipid substrates to the respiratory chain, reducing electron leak and ROS production. This metabolon maintains Q levels, minimizes QH2-reductive stress, and improves OXPHOS efficiency. Muscle-specific ETFDH-/- mice develop myopathy due to CIII dysfunction, indicating that ETFDH is a required OXPHOS component and a potential therapeutic target for mitochondrial redox medicine

INSTRUMENT(S): Orbitrap Exploris 240

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Skeletal Muscle

SUBMITTER: Alberto Paradela

LAB HEAD: Laura Formentini

PROVIDER: PXD045351 | Pride | 2023-10-24

REPOSITORIES: Pride

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			Action	DRS
	20230607_LFormentini_PROT1967_HEK-COQ2.mzML	Mzml
	20230607_LFormentini_PROT1967_HEK-COQ2.mzid.gz	Mzid
	20230607_LFormentini_PROT1967_HEK-COQ2.raw	Raw
	20230607_LFormentini_PROT1967_Skm-COQ2.raw	Raw
	20230607_LFormentini_PROT1967_Skm-ETFDH.raw	Raw

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