AUTHOR=Liu Peiduo , Chang Kai , Requejo Guillermo , Bai Hua 

TITLE=mTORC2 protects the heart from high-fat diet-induced cardiomyopathy through mitochondrial fission in Drosophila

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.866210

DOI=10.3389/fcell.2022.866210

ISSN=2296-634X

ABSTRACT=<p>High-fat diet (HFD)-induced obesity has become the major risk factor for the development of cardiovascular diseases, but the underlying mechanisms remain poorly understood. Here, we use <italic>Drosophila</italic> as a model to study the role of mTORC2 in HFD-induced mitochondrial fission and cardiac dysfunction. We find that knockdown of mTORC2 subunit <italic>rictor</italic> blocks HFD-induced mitochondrial fragmentation and Drp1 recruitment. Knockdown of <italic>rictor</italic> further impairs cardiac contractile function under HFD treatment. Surprisingly, knockdown of <italic>Akt</italic>, the major effector of mTORC2, did not affect HFD-induced mitochondrial fission. Similar to mTORC2 inhibition, knockdown of <italic>Drp1</italic> blocks HFD-induced mitochondrial fragmentation and induces contractile defects. Furthermore, overexpression of <italic>Drp1</italic> restored HFD-induced mitochondrial fragmentation in <italic>rictor</italic> knockdown flies. Thus, we uncover a novel function of mTORC2 in protecting the heart from HFD treatment through Drp1-dependent mitochondrial fission.</p>