Targeting Mitochondrial Fission-Fusion Imbalance in Heart Failure
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IMMUNOMETABOLISM (NOS CÂMARA, SECTION EDITOR)
Targeting Mitochondrial Fission-Fusion Imbalance in Heart Failure Thiago N. Menezes 1 & Lisley S. Ramalho 1 & Luiz R. G. Bechara 1 & Julio Cesar Batista Ferreira 1,2,3 Accepted: 14 October 2020 # Springer Nature Switzerland AG 2020
Abstract Purpose of the Review This review focuses on the central role of mitochondrial fission-fusion imbalance in heart failure. We also discuss the development of pharmacological strategies capable of re-establishing mitochondrial dynamics in heart failure. Recent Findings Heart failure is a degenerative disease and a major cause of morbidity and mortality worldwide. Loss of mitochondrial fission-fusion balance and consequent impaired cardiac bioenergetics are hallmarks of heart failure. Therefore, the identification of maladaptive molecular signatures that contribute to impaired mitochondrial dynamics and bioenergetics, such as activation of protein kinase C βII, becomes a valuable platform and strategy to generate novel, and more effective, pharmacological tools to treat heart failure. Summary Here, we discuss critical post-translational modifications (phosphorylation) of mitochondrial dynamics-related proteins in failing hearts. We also highlight some druggable protein-protein interactions that control mitochondrial dynamics as potential targets to treat heart failure. Keywords Cell signaling . Metabolism . Oxidative Stress . Protein Kinase C . Mitofusin . Mitochondria
Introduction Heart failure is a chronic and progressive degenerative syndrome in which the heart is unable to pump the required amount of blood to supply the whole-body demand for oxygen and nutrients. It is a major public health problem, affecting over 25 million people worldwide [1]. The most common causes of heart failure are ischemic heart disease, hypertension, and valvular heart diseases. Chagas’s disease is one of the main causes of heart failure in tropical developing countries [2]. The pathophysiology of heart failure is characterized by biochemical, morphological, and functional changes in the heart that progressively contributes to reduced quality of life and survival of patients. Half of heart failure patients display reduced left This article is part of the Topical Collection on Immunometabolism * Julio Cesar Batista Ferreira [email protected] 1
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
2
Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA
3
Departamento de Anatomia, Instituto de Ciências Biomédicas da Universidade de São Paulo, Av. Professor Lineu Prestes, 2415, São Paulo, SP-CEP 05508-000, Brazil
ventricular ejection fraction, termed HFrEF (heart failure with reduced ejection fraction), and the other half present preserved left ventricular ejection fraction, termed HFpEF (heart failure with preserved ejection fraction) [2, 3]. Most of the available therapies for heart failure were developed to treat HFrEF, but not HFpEF [2–5]. Considering these
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