Sex‐specific mitochondrial dynamics and mitophagy response to muscle damage

Abstract

Muscle damage imposes stress on mitochondria resulting in mitochondrial fusion, fission, and mitophagy. Testosterone is a regulator of these processes. However, no study has examined the effect of sex‐specific resistance exercise (RE)‐induced hormonal response on mitochondrial dynamics and mitophagy after muscle damage in untrained men and women. Untrained men and women performed two sessions of 80 unilateral maximal eccentric knee extensions (ECC) followed by upper‐body RE (ECC+RE) aimed to induce hormonal changes and maintain a similar lower body demands between conditions or 20 min seated rest (ECC+REST). Vastus lateralis samples were analyzed for gene and protein expression of OPA1, MFN1, DRP1, PINK1, and Parkin at baseline (BL), 12 and 24 h. Testosterone area under the curve was greater for ECC+RE than ECC+REST in men and was greater in men than women for both conditions. A significant time × sex × condition effect was found for Parkin protein expression. At 12 and 24 h, Parkin was lower for ECC + REST than ECC + RE for men; whereas, Parkin was increased at 24 h for women regardless of condition. A significant time effect was found for OPA1 protein expression increasing at 12 and 24 h. A significant time × sex × condition effects were found for MFN1 , DRP1 , and PINK1 gene expression with increases at 12 h in men for ECC + RE. A significant time × sex effect was found for OPA1 gene expression with a decrease at 12 h in men, and 12 h expression in men was lower than women. RE‐induced hormonal changes promoted expression of fission, fusion, and mitophagy markers in men. With muscle damage, regardless of condition, expression of inner mitochondrial membrane fusion markers are promoted in both sexes; whereas, those for mitophagy were promoted in women but reduced in men.

Sex Differences in the Skeletal Muscle Response to a High Fat, High Sucrose Diet in Rats

“…Sex differences in mitochondrial dynamics have been reported after eccentric resistance training. MFN1, DRP1, and PINK1 were greater in men than in women, authors attributed these differences to sex hormones [43]. In response to the HFHS diet, we observed no evidence of differences in these key elements of mitochondrial dynamics or the upstream signaling molecule sirtuin1 at 14 weeks.…”

TOMM40 regulates hepatocellular and plasma lipid metabolism via an LXR-dependent pathway

“…For example, mediators of LD formation located outside of MERCs, including FITM2, regulate the budding of LDs from ER into the cytosol 65 , and coalescence of LDs is promoted by the CIDE family of proteins (aka FSP27) 66,67 . Additionally, it is notable that sex hormones including estrogen, have been reported to transcriptionally regulate genes involved in mitochondrial dynamics and mitophagy, including MFN2 expression, which may further explain the differential effects of Tomm40 KD on MERCs and mito-LD contact sites between male and female mouse livers 68,69 .…”