ArticleThe Journal of clinical investigation2019
An alternative mitophagy pathway mediated by Rab9 protects the heart against ischemia.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers, 3 of them syntheses that pooled it.
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Who cites it
179 citing papers in PubMed, 3 syntheses or guidelines pooled it, 242 citations in OpenAlex.
- Mitochondrial dysfunction in cardiovascular disease: Towards exercise regulation of mitochondrial function.Frontiers in physiology · 2023Pooled it
- Emerging roles of ATG7 in human health and disease.EMBO molecular medicine · 2021Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Mitophagy in cisplatin-induced kidney injury: regulatory mechanisms and therapeutic targets.Annals of medicine · 2026Review
- Emerging mechanisms of ATG8-independent non-canonical autophagy.Journal of physiology and biochemistry · 2026Review
- Mitophagy in pathogenesis and therapeutic implications for infection.Experimental & molecular medicine · 2026Review
- Mitophagy Facilitates Cytosolic Proteostasis to Preserve Cardiac Function.Circulation research · 2026Article
- Disrupted Mitochondrial Quality Control in Atherosclerotic Disease: Mitophagy and Dynamics in Focus.JACC. Basic to translational science · 2026Review
- Mechanism of Yangxin Dawa Yimixike Mi Gao for myocardial ischemia/reperfusion injury: an integrative study of network pharmacology and and validation.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Article
- Mitochondrial oxidative stress, calcium and dynamics in cardiac ischaemia-reperfusion injury.The Journal of physiology · 2026Review
- Puerarin alleviates myocardial ischemia-reperfusion injury by enhancing FUNDC1-mediated mitophagy.Molecular and cellular biochemistry · 2026Article
- Residual cardiovascular risk in coronary artery disease: from pathophysiology to established and novel therapies.Nature reviews. Cardiology · 2026Review
- Divergent Role of ULK1 to Balance Mitochondrial Homeostasis and Bioenergetics in Ovarian Cancer Spheroids.Cancers · 2026Article
- Allyl-substituted ALT001 promotes alternative mitophagy and improves therapeutic outcomes in Alzheimer's disease models.Scientific reports · 2026Article
- Two Routes for Removing Unhealthy Mitochondria: Degradation and Secretion.Circulation research · 2026Review
- Intercellular Mitochondrial Transfer: Implications in Cardiovascular Health.Circulation research · 2026Review
- Rethinking Mitochondria: The Extracellular Dimension.Circulation research · 2026Review
- Melatonin and mitochondrial protection in cardiac ischemia-reperfusion injury: mechanisms, evidence and translational perspectives.Basic research in cardiology · 2026Review
- Rab12 is a regulator of mitophagy and mitochondrial homeostasis.bioRxiv : the preprint server for biology · 2026Article
- Biomarkers of Cardiac Metabolic Flexibility in Health, HFrEF and HFpEF.International journal of molecular sciences · 2026Review
119 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
Energy stress, such as ischemia, induces mitochondrial damage and death in the heart. Degradation of damaged mitochondria by mitophagy is essential for the maintenance of healthy mitochondria and survival. Here, we show that mitophagy during myocardial ischemia was mediated predominantly through autophagy characterized by Rab9-associated autophagosomes, rather than the well-characterized form of autophagy that is dependent on the autophagy-related 7 (Atg) conjugation system and LC3. This form of mitophagy played an essential role in protecting the heart against ischemia and was mediated by a protein complex consisting of unc-51 like kinase 1 (Ulk1), Rab9, receptor-interacting serine/thronine protein kinase 1 (Rip1), and dynamin-related protein 1 (Drp1). This complex allowed the recruitment of trans-Golgi membranes associated with Rab9 to damaged mitochondria through S179 phosphorylation of Rab9 by Ulk1 and S616 phosphorylation of Drp1 by Rip1. Knockin of Rab9 (S179A) abolished mitophagy and exacerbated the injury in response to myocardial ischemia, without affecting conventional autophagy. Mitophagy mediated through the Ulk1/Rab9/Rip1/Drp1 pathway protected the heart against ischemia by maintaining healthy mitochondria.
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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.