Dietary schizophyllan reduces mitochondrial damage by activating SIRT3 in mice

Abstract

Schizophyllan (SPG), produced by Schizophyllumcommune, is an exopolysaccharide with multiple academicand commercial uses, including in the food industryand for various medical functions. We previously demonstratedthat SPG conjugated with c-Src peptide exerted asignificant therapeutic effect on mouse models of the acuteinflammatory diseases polymicrobial sepsis and ulcerativecolitis. Here we extended these results by investigatingwhether SPG exerted a protective effect against mitochondrialdamage in the liver via sirtuin 3 (SIRT3) induction,focusing on the deacetylation of succinate dehydrogenase A(SDHA) and superoxide dismutase 2 (SOD2). Liver damagemodels induced by alcohol or conjugated linoleic acid (CLA,which simulates lipodystrophy) in SIRT3−/−,SOD2−/−,andSDHA−/−mice were used. Results showed that dietary supplementationwith SPG induced SIRT3 activation; this wasinvolved in mitochondrial metabolic resuscitation that counteredthe adverse effects of alcoholic liver disease and CLAinduceddamage. The mitochondrial SIRT3 mediated thedeacetylation and activation of SOD2 in the liver and SDHA in adipose tissues, suggesting that SPG supplementationreduced ethanol-induced liver damage and CLA-inducedadverse dietary effects via SIRT3–SOD2 and SIRT3–SDHAsignaling, respectively. Together, these results suggest thatdietary SPG has a previously unrecognized role in SIRT3-mediated mitochondrial metabolic resuscitation duringmitochondria-related diseases.