Ulk1/Rab9-mediated alternative mitophagy confers cardioprotection during energy stress
Rimpy Dhingra,1 Inna Rabinovich-Nikitin,1 and Lorrie A. Kirshenbaum1,2
1The Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, and
2Rady College of Medicine, Max Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
Address correspondence to: Lorrie A. Kirshenbaum, Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Rm. 3016, 351 Taché Avenue, Winnipeg, Manitoba, Canada, R2H 2A6. Phone: 204.235.3661; Email: Lorrie@sbrc.ca.
Find articles by Dhingra, R. in: JCI | PubMed | Google Scholar
1The Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, and
2Rady College of Medicine, Max Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
Address correspondence to: Lorrie A. Kirshenbaum, Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Rm. 3016, 351 Taché Avenue, Winnipeg, Manitoba, Canada, R2H 2A6. Phone: 204.235.3661; Email: Lorrie@sbrc.ca.
Find articles by Rabinovich-Nikitin, I. in: JCI | PubMed | Google Scholar
1The Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, and
2Rady College of Medicine, Max Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
Address correspondence to: Lorrie A. Kirshenbaum, Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Rm. 3016, 351 Taché Avenue, Winnipeg, Manitoba, Canada, R2H 2A6. Phone: 204.235.3661; Email: Lorrie@sbrc.ca.
Find articles by Kirshenbaum, L. in: JCI | PubMed | Google Scholar
First published January 22, 2019 - More info
J Clin Invest. 2019;129(2):509–512. https://doi.org/10.1172/JCI125980.
Copyright © 2019, American Society for Clinical Investigation
The heart relies on mitochondria-derived energy production for continuous contraction and relaxation; therefore, the maintenance of a pool of healthy mitochondria is essential for sustaining normal cardiac performance. Mitophagy serves as a critical process for maintaining mitochondrial quality control and involves the PTEN-induced kinase 1/Parkin (Pink1/Parkin) pathway and autophagosomes labeled with the autophagy proteins autophagy-related 7 (ATG) and light chain 3 (LC3). In this issue of the JCI, Saito and colleagues identify an alternative pathway for mitophagy that utilizes the serine/threonine protein kinase Unc-51–like kinase 1 (Ulk1) and the small GTPase Rab9 to clear damaged mitochondria independently of conventional autophagy proteins. Together, the results of this study reveal that Ulk1 phosphorylation of Rab9 at serine 179 is critical for alternative mitophagy and cardioprotection under energy stress conditions.
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