Galanin promotes autophagy and alleviates apoptosis in the hypertrophied heart through FoxO1 pathway
Ilenia Martinelli,
Andrei Timotin,
Paula Moreno-Corchado,
Dimitri Marsal,
Solomiia Kramar,
Halina Loy,
Carine Joffre,
Frederic Boal,
Helene Tronchere,
Oksana Kunduzova
Affiliations
Ilenia Martinelli
National Institute of Health and Medical Research (INSERM) U1048, 31432, Toulouse, Cedex 4, France; Paul Sabatier University, 31062, Toulouse, Cedex 9, France
Andrei Timotin
National Institute of Health and Medical Research (INSERM) U1048, 31432, Toulouse, Cedex 4, France; Paul Sabatier University, 31062, Toulouse, Cedex 9, France
Paula Moreno-Corchado
National Institute of Health and Medical Research (INSERM) U1048, 31432, Toulouse, Cedex 4, France; Paul Sabatier University, 31062, Toulouse, Cedex 9, France
Dimitri Marsal
National Institute of Health and Medical Research (INSERM) U1048, 31432, Toulouse, Cedex 4, France; Paul Sabatier University, 31062, Toulouse, Cedex 9, France
Solomiia Kramar
National Institute of Health and Medical Research (INSERM) U1048, 31432, Toulouse, Cedex 4, France; Paul Sabatier University, 31062, Toulouse, Cedex 9, France
Halina Loy
National Institute of Health and Medical Research (INSERM) U1048, 31432, Toulouse, Cedex 4, France; Paul Sabatier University, 31062, Toulouse, Cedex 9, France
Carine Joffre
Paul Sabatier University, 31062, Toulouse, Cedex 9, France; Centre de Recherches en Cancérologie de Toulouse (CRCT), 2 Avenue Hubert Curien, 31037, Toulouse, France
Frederic Boal
National Institute of Health and Medical Research (INSERM) U1048, 31432, Toulouse, Cedex 4, France; Paul Sabatier University, 31062, Toulouse, Cedex 9, France
Helene Tronchere
National Institute of Health and Medical Research (INSERM) U1048, 31432, Toulouse, Cedex 4, France; Paul Sabatier University, 31062, Toulouse, Cedex 9, France
Oksana Kunduzova
National Institute of Health and Medical Research (INSERM) U1048, 31432, Toulouse, Cedex 4, France; Paul Sabatier University, 31062, Toulouse, Cedex 9, France; Corresponding author. INSERM, U1048, 1 av. J Poulhès, 31432, Toulouse, Cedex 4, France.
Autophagy and apoptosis are powerful regulators of multiple facets of cellular metabolism and homeostasis. Here, we uncover that galanin, a pleiotropic peptide, regulates cardiac autophagy and deactivates apoptotic cell death through the Forkhead box protein O1 (FoxO1) pathway. In hypertrophied heart, galanin promotes autophagy and metabolic shift from fatty acid (FA) to glucose oxidation and preserves mitochondrial integrity. In cardiomyoblasts, galanin triggers autophagosome formation and alleviates hypertrophy, apoptotic cell death, and mitochondrial stress. Mechanistically, galanin dictates cell autophagic and anti-apoptotic phenotypes through FoxO1 pathway. Together, these findings uncover a previously unknown role for galanin in the regulation of cardiac autophagy and provide new insights into the molecular mechanisms supporting cell survival in the hypertrophic reprogramming of the heart.
