{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T20:11:23Z","timestamp":1788811883572,"version":"build-2803163510"},"reference-count":41,"publisher":"Institute of Physiology of the Czech Academy of Sciences","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Physiol Res"],"abstract":"<jats:p>Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a major cause of cirrhosis, liver cancer, and cardiovascular disease. Early mitochondrial dysfunction drives lipid imbalance, inflammation, and fibrosis. Given the lack of approved pharmacological treatments, this study compares the mitochondria-targeted agents MitoQ and SS-31 for their effects on mitochondrial function, oxidative stress, apoptosis, and inflammation in aged, nutritionally stressed mice with MASLD. Aged female C57BL\/6 mice (12\u201314 months) were fed a high-fat, high-fructose diet for 16 weeks to induce MASLD. Mice were randomized into four groups: (i) control diet, (ii) MASLD, (iii) MASLD + MitoQ (25 mg\/kg\/day, oral), and (iv) MASLD + SS-31 (3 mg\/kg\/day, i.p.). Liver tissues were analyzed by western blotting for mitochondrial biogenesis and dynamics markers (PGC-1\u03b1, NRF1, and TFAM), oxidative stress regulators (SOD2, Nrf2, 4-HNE), apoptosis-related proteins (Bax, and Bcl-2), inflammatory and fibrotic mediators (NF-\u03baB, and NLRP3), and insulin signaling proteins (p-Akt, and GLUT2). Both MitoQ and SS-31 significantly improved mitochondrial protein expression and overall liver health compared with untreated MASLD mice. MitoQ primarily enhanced mitochondrial antioxidant defenses by upregulating SOD2 and Nrf2 while decreasing 4-HNE adduct formation, reflecting reduced oxidative damage. SS-31, in contrast, more effectively preserved mitochondrial structural integrity. Both compounds attenuated inflammation by suppressing NF-\u03baB and NLRP3 activation. They also improved insulin sensitivity by increasing p-Akt and GLUT2 expression. Histological analysis using H&amp;E staining revealed marked reductions in hepatic steatosis. Mitochondrial dysfunction drives MASLD progression. In aged MASLD mice, MitoQ enhances antioxidant defense, SS-31 preserves integrity, and both improve insulin signaling and reduce fibrosis, supporting mitochondrial therapy for MASLD.<\/jats:p>","DOI":"10.33549\/physiolres.935810","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T19:25:44Z","timestamp":1788809144000},"page":"699","source":"Crossref","is-referenced-by-count":0,"title":["Targeting Mitochondria in MASLD: Comparative Evaluation of MitoQ and SS-31 (Elamipretide) in Aged Female Mice under Nutritional Stress"],"prefix":"10.33549","volume":"75","author":[{"given":"Di","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Hepatology, Public Health Clinical Center Affiliated to Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxing","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajad","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changfei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"19169","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref0","doi-asserted-by":"crossref","unstructured":"1.\tBawiskar N, Acharya S, Kumar S. 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