ArticleBone research2025
Sirtuin 5-mediated desuccinylation of Slc25a4 inhibits osteoporosis by enhancing mitochondrial respiration.
Article in Bone research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
2 citing papers in PubMed.
- Protein acylation and bone metabolism: bidirectional crosstalk linking metabolic reprogramming to skeletal homeostasis.Journal of molecular histology · 2026Review
- Mechanistic and functional integration of sirtuin deacylases: from substrate specificity to biological outcomes.Glycoconjugate journal · 2026Review
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Osteoporosis is a prevalent metabolic bone disorder that develops when osteoclast-mediated bone resorption chronically exceeds osteoblast-driven bone formation. The molecular pathways that govern osteogenic dysfunction and connect cellular metabolism to differentiation regulation remain poorly characterized. Here, we identify Sirtuin 5 (Sirt5) as a pivotal osteogenic regulator through bioinformatic screening and functional validation in Sirt5-knockout mice. Mechanistically, Sirt5 governs mitochondrial homeostasis by desuccinylating Solute Carrier Family 25 Member 4 (Slc25a4) at lysine 147 (K147), as demonstrated by quantitative succinylome profiling and site-directed mutagenesis. This site-specific desuccinylation triggers Slc25a4 degradation, attenuating mitochondrial oxidative stress and promoting osteoblast differentiation. Crucially, Slc25a4-K147 succinylation drives osteoporosis progression, while Sirt5-mediated desuccinylation at this site confers protection. Our work reveals the Sirt5-Slc25a4-K147 axis as a novel regulatory mechanism coupling mitochondrial metabolism to bone homeostasis, offering a therapeutic target for osteoporosis intervention.
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Registered trials
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