What this means
Researchers found MOTS-c helped protect kidneys in mice with diabetes, and in human kidney cells. This is early work, and it does not show that MOTS-c would help people.
Plain-English summary written by an AI model from the abstract. The original is below.
- Who it was tested in
- Mice with diabetes, human kidney cells in a lab, and cells in a dish
- Kind of research
- A study
The science
- Original title
- Mots-c attenuates diabetic nephropathy by downregulating LARS1 to promote lipophagy and suppress tubular senescence.
- Authors
- Wang J, Luo S, Han Y et al.
- Journal
- Biochemical pharmacology
- Published
- Oct 23, 2026
- Study type
- Study
- PMID
- 42918312 ↗
Abstract
Diabetic nephropathy (DN) is a leading cause of end-stage kidney disease, but current therapies do not halt its progression. Mitochondrial-derived peptides have garnered attention for their roles in metabolic regulation, yet whether Mitochondrial Open Reading Frame of the 12S rRNA-c (MOTS-c) participates in DN pathogenesis has not been fully elucidated. In this study, MOTS-c treatment led to dose-dependent preservation of urinary albumin-to-creatinine ratio (UACR), accompanied by attenuated tubular injury, diminished lipid deposition, and reduced macrophage accumulation. Transcriptomic analyses revealed significant enrichment of pathways related to senescence and lipid metabolism. Moreover, MOTS-c suppressed p16INK4A, γH2AX, and SA-β-gal activity, while restoring lipid homeostasis through regulation of CPT1A and ADRP. Mechanistically, MOTS-c downregulated LARS1, an established negative modulator of lipophagy, thereby facilitating LC3-mediated clearance of lipid droplets (LDs). LARS1 overexpression in HK-2 cells effectively abrogated these protective phenotypes. Furthermore, co-administration of the autophagy inhibitor 3-MA in db/db mice largely reversed the renoprotective effects of MOTS-c, supporting the functional relevance of lipophagy in this process. Our findings indicate that MOTS-c protects against diabetic kidney injury by downregulating LARS1, thereby promoting lipophagy, reducing lipid deposition, and suppressing tubular senescence. Targeting the LARS1-lipophagy-senescence axis may offer a new strategy for DN treatment.
Wang J, Luo S, Han Y et al. Mots-c attenuates diabetic nephropathy by downregulating LARS1 to promote lipophagy and suppress tubular senescence. Biochemical pharmacology. 2026. doi:10.1016/j.bcp.2026.118572. PMID: 42918312. https://pubmed.ncbi.nlm.nih.gov/42918312/
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