Mitochondrial Sirt3 in Kidney Aging: Sex-Specific Links to Metabolic Homeostasis and Oxidative Stress

Šimunić, Ena; Šešelja, Kate; Podgorski, Iva I.; Pinterić, Marija; Belužić, Robert; Popović Hadžija, Marijana; Balog, Tihomir; Habisch, Hansjörg; Madl, Tobias; Sobočanec, Sandra (2025) Mitochondrial Sirt3 in Kidney Aging: Sex-Specific Links to Metabolic Homeostasis and Oxidative Stress. RedoXplore, 2 (1). ISSN 3042-1772

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Abstract

Purpose: Aging is a complex biological process that begins at the cellular level, disrupting energy homeostasis. This study investigated the role of Sirt3, major mitochondrial deacetylase involved in metabolic pathways, in sex-dependent changes in energy homeostasis during aging in kidney of Sirt3 WT and KO mice. Methods: Enzymatic activity, lipid peroxidation, protein carbonylation with Western blot and metabolomic analyses were performed to assess physiological and metabolic parameters Results: Higher Sirt3 expression in male WT mice leads to increased vulnerability to its deficiency, as reflected in the shorter lifespan of male KO mice. This is further supported by distinct metabolomic clustering in male KO mice, highlighting significant metabolic disruptions. Male-specific declines in metabolites such as creatine, phosphorylcholine, trimethylamine-N-oxide, and L-carnitine, along with reduced trifunctional multienzyme complex subunit β (HADHB) expression, point to impaired fatty acid metabolism and mitochondrial dysfunction. Conclusions: The findings emphasize the sex-specific function of Sirt3 in regulating mitochondrial activity, energy metabolism, and oxidative stress in the murine kidney, with male mice exhibiting a greater reliance on Sirt3 for metabolic stability.

Item Type:	Article
Uncontrolled Keywords:	Sirtuin 3; sex differences; murine kidney; aging; oxidative stress
Subjects:	BIOMEDICINE AND HEALTHCARE
Divisions:	Division of Molecular Medicine
Depositing User:	Sandra Sobočanec
Date Deposited:	10 Nov 2025 14:15
URI:	http://fulir.irb.hr/id/eprint/10175
DOI:	10.70200/RX202501001S

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