Dataset Information

ETFDH comigrates with CIII in BN-PAGE

ABSTRACT: Proteomic analysis of 13 bands from BN-PAGE immunostaining of mouse skeletal muscle mitochondrial proteins: 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

DISEASE(S): Myopathy

SUBMITTER: Alberto Paradela

LAB HEAD: Laura Formentini

PROVIDER: PXD045352 | Pride | 2023-10-24

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20230622_LauraFormentini_PROT1982_band_01.raw	Raw
	20230622_LauraFormentini_PROT1982_band_02.raw	Raw
	20230622_LauraFormentini_PROT1982_band_03.raw	Raw
	20230622_LauraFormentini_PROT1982_band_04.raw	Raw
	20230622_LauraFormentini_PROT1982_band_05.raw	Raw

Items per page:

1 - 5 of 14

Similar Datasets

Project description:Aims/hypothesis: While lipid deposition in skeletal muscle is considered to be involved in obesity-associated insulin resistance, neutral intramyocellular lipid (IMCL) accumulation per se does not necessarily induce insulin resistance. We previously demonstrated that overexpression of the lipid droplet coat protein perilipin 2 augments intramyocellular lipid content while improving insulin sensitivity. Another member of the perilipin family, perilipin 5 (PLIN5), is predominantly expressed in oxidative tissues like skeletal muscle. Here we investigated the effects of PLIN5 overexpression M-bM-^@M-^S in comparison with effects of PLIN2 M-bM-^@M-^S on skeletal muscle lipid levels, gene expression profiles and insulin sensitivity. Methods: Gene electroporation was used to overexpress PLIN5 in tibialis anterior muscle of rats fed a high fat diet. Eight days after electroporation, insulin-mediated glucose uptake in skeletal muscle was measured by means of a hyperinsulinemic euglycemic clamp. Electron microscopy, fluorescence microscopy and lipid extractions were performed to investigate IMCL accumulation. Gene expression profiles were obtained using microarrays. Results: TAG storage and lipid droplet size increased upon PLIN5 overexpression. Despite the higher IMCL content, insulin sensitivity was not impaired and DAG and acylcarnitine levels were unaffected. In contrast to the effects of PLIN2 overexpression, microarray data analysis revealed a gene expression profile favoring FA oxidation and improved mitochondrial function. Conclusions/interpretation: Both PLIN2 and PLIN5 increase neutral IMCL content without impeding insulin-mediated glucose uptake. As opposed to the effects of PLIN2 overexpression, overexpression of PLIN5 in skeletal muscle promoted expression of a cluster of genes under control of PPARM-NM-1 and PGC1M-NM-1 involved in FA catabolism and mitochondrial oxidation. Rats received a high fat diet for 3 weeks; 2 weeks after start of the diet intervention Plin5 (OXPAT) or Plin2 (ADRP) were overexpressed in either the right or left tibialis anterior muscle. One week later pooled tibialis anterior muscle samples were analysed on microarrays.

Dataset Information

ETFDH comigrates with CIII in BN-PAGE

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets