Abstract P2080: Role Of Atg9 Proteins In Regulating Autophagosome Formation

• Published in: Circulation research Vol. 131; no. Suppl_1
• Main Authors: Diao, Rachel Y, Liang, Wenjing, Chi, Liguo, Fang, Xi, Gustafsson, Asa
• Format: Journal Article
• Language: English
• Published: 05.08.2022
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/res.131.suppl_1.P2080

Abstract only Cardiac myocytes require large amounts of energy generated by mitochondria to sustain contraction, and there is a strong link between mitochondrial dysfunction and heart disease. Defective mitochondria are less efficient at generating ATP, produce excessive reactive oxygen species, and release pro-apoptotic proteins, all of which can lead to loss of cardiac myocytes and reduced ability to sustain contractile function. Therefore, mitochondrial quality control is critical in preventing mitochondria from causing harm to the cell. Selective autophagy of the mitochondria (mitophagy) is the primary mechanism responsible for eliminating dysfunctional mitochondria. Despite intense research focus on mitophagy over the past decade, little is still known about early events in the pathway, and the signals that orchestrate the selective recruitment of the autophagic machinery to dysfunctional mitochondria are unclear. It is known that autophagosome formation requires Atg9, which is embedded in small Golgi-derived vesicles. To date, most data on Atg9 are from yeast and our knowledge of mammalian Atg9a and Atg9b functions in cells and tissues are still limited. Here, we found that Atg9a and Atg9b are expressed in the heart and that both proteins are increased in the infarct border zone after ligation of the LAD. We also discovered that Atg9a and Atg9b are present on distinct vesicles in myocytes. Atg9b-positive vesicles are localized throughout the cytosol, whereas Atg9a-positive vesicles are associated with the mitochondria even under basal conditions. This suggests that they might have distinct functions and that Atg9a may play a more selective role at the mitochondria. Interestingly, Atg9a, but not Atg9b, is degraded by the proteasome upon activation of mitophagy, a potential indication that this may be a mechanism to prevent excessive mitophagy. Overall, our findings suggest that Atg9a and Atg9b play distinct roles in autophagy and mitophagy and that the mitochondrial localization of Atg9a allows it to initiate autophagosome formation more efficiently during mitophagy.