ArticleAutophagy2015
SIRT5 regulation of ammonia-induced autophagy and mitophagy.
Article in Autophagy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 202 papers, 3 of them syntheses that pooled it.
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Who cites it
202 citing papers in PubMed, 3 syntheses or guidelines pooled it, 327 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Physical exercise for people with cirrhosis.The Cochrane database of systematic reviews · 2018Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- KRAS/ERK2-driven stabilization of AARS1 reprograms tumor metabolism and confers Sorafenib resistance in lung adenocarcinoma.Cell death and differentiation · 2026Article
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- Review
- The Sirtuin Network: Linking NADDiabetes/metabolism research and reviews · 2026Review
- Epidemiological characteristics of Echinococcus granulosus infection in children from some sites in Xinjiang and its association with platelets.BMC infectious diseases · 2026Article
- MoCox6 is a regulator of mitophagy and a druggable target in Magnaporthe oryzae.Nature microbiology · 2026Article
- SIRT5-dependent desuccinylation licenses UBR5-mediated degradation of TAMM41 to regulate mitochondrial metabolism in lung adenocarcinoma.Biology direct · 2026Article
- Beyond deacetylation: crosstalk mechanisms and context-dependent regulation of sirtuin non-classical enzymatic functions in disease.Molecular medicine (Cambridge, Mass.) · 2026Review
- SIRT4 positively regulates autophagy via ULK1, but independently of HDAC6 and OPA1.FEBS open bio · 2026Article
- SIRT5-RNF126 coordinated regulation of METTL17 stability controls mitochondrial function and glioma progression.Cell & bioscience · 2026Article
- Unveiling the importance of SIRT5 for cardiac health and disease in an era of increasing longevity.GeroScience · 2026Review
- The role and therapeutic potential of succinate and succinylation in cardiovascular diseases.Clinical epigenetics · 2026Review
- SIRT5-RAC2 Axis Drives Monocyte-to-Macrophage Differentiation to Promote Inflammatory Injury in Premature Ovarian Insufficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Succinylation: A Functional Nexus Between Metabolic Reprogramming and Epigenetic Modifications in Cancer.Molecules (Basel, Switzerland) · 2026Review
- MaR1 and NGF combine to inhibit autophagy through the GSK-3β/β-catenin pathway to promote sciatic nerve repair.Journal of translational medicine · 2026Article
- Processes and therapeutic perspectives of acylation modifications of lysine and cysteine in tumors.Cell communication and signaling : CCS · 2026Review
- Mitophagy and oxidative stress in chronic kidney disease (Review).Molecular medicine reports · 2026Review
142 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In liver the mitochondrial sirtuin, SIRT5, controls ammonia detoxification by regulating CPS1, the first enzyme of the urea cycle. However, while SIRT5 is ubiquitously expressed, urea cycle and CPS1 are only present in the liver and, to a minor extent, in the kidney. To address the possibility that SIRT5 is involved in ammonia production also in nonliver cells, clones of human breast cancer cell lines MDA-MB-231 and mouse myoblast C2C12, overexpressing or silenced for SIRT5 were produced. Our results show that ammonia production increased in SIRT5-silenced and decreased in SIRT5-overexpressing cells. We also obtained the same ammonia increase when using a new specific inhibitor of SIRT5 called MC3482. SIRT5 regulates ammonia production by controlling glutamine metabolism. In fact, in the mitochondria, glutamine is transformed in glutamate by the enzyme glutaminase, a reaction producing ammonia. We found that SIRT5 and glutaminase coimmunoprecipitated and that SIRT5 inhibition resulted in an increased succinylation of glutaminase. We next determined that autophagy and mitophagy were increased by ammonia by measuring autophagic proteolysis of long-lived proteins, increase of autophagy markers MAP1LC3B, GABARAP, and GABARAPL2, mitophagy markers BNIP3 and the PINK1-PARK2 system as well as mitochondrial morphology and dynamics. We observed that autophagy and mitophagy increased in SIRT5-silenced cells and in WT cells treated with MC3482 and decreased in SIRT5-overexpressing cells. Moreover, glutaminase inhibition or glutamine withdrawal completely prevented autophagy. In conclusion we propose that the role of SIRT5 in nonliver cells is to regulate ammonia production and ammonia-induced autophagy by regulating glutamine metabolism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.