Sex-specific Genetic Regulation of Adipose Mitochondria and Metabolic Syndrome by Ndufv2

Overview

Journal Nat Metab

Publisher Springer Nature

Specialty Endocrinology

Date 2021 Oct 26

PMID 34697471

Citations 26

Authors

Karthickeyan Chella Krishnan

Laurent Vergnes

Rebeca Acin-Perez

Linsey Stiles

Michael Shum

Lijiang Ma

Etienne Mouisel

Calvin Pan

Timothy M Moore

Miklos Peterfy

Casey E Romanoski

Karen Reue

Johan L M Bjorkegren

Markku Laakso

Marc Liesa

Aldons J Lusis

Affiliations

Soon will be listed here.

Abstract

We have previously suggested a central role for mitochondria in the observed sex differences in metabolic traits. However, the mechanisms by which sex differences affect adipose mitochondrial function and metabolic syndrome are unclear. Here we show that in both mice and humans, adipose mitochondrial functions are elevated in females and are strongly associated with adiposity, insulin resistance and plasma lipids. Using a panel of diverse inbred strains of mice, we identify a genetic locus on mouse chromosome 17 that controls mitochondrial mass and function in adipose tissue in a sex- and tissue-specific manner. This locus contains Ndufv2 and regulates the expression of at least 89 mitochondrial genes in females, including oxidative phosphorylation genes and those related to mitochondrial DNA content. Overexpression studies indicate that Ndufv2 mediates these effects by regulating supercomplex assembly and elevating mitochondrial reactive oxygen species production, which generates a signal that increases mitochondrial biogenesis.

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