Mitochondrial Chaperones and Proteases in Cardiomyocytes and Heart Failure

Abstract

Heart failure is one of the leading causes of morbidity and mortality worldwide. In cardiomyocytes, mitochondria are not only essential organelles providing more than 90% of the ATP necessary for contraction, but they also play critical roles in regulating intracellular Ca2+ signaling, lipid metabolism, production of reactive oxygen species (ROS), and apoptosis. Because mitochondrial DNA only encodes 13 proteins, most mitochondrial proteins are nuclear DNA-encoded, synthesized, and transported from the cytoplasm, refolded in the matrix to function alone or as a part of a complex, and degraded if damaged or incorrectly folded. Mitochondria possess a set of endogenous chaperones and proteases to maintain mitochondrial protein homeostasis. Perturbation of mitochondrial protein homeostasis usually precedes disruption of the whole mitochondrial quality control system and is recognized as one of the hallmarks of cardiomyocyte dysfunction and death. In this review, we focus on mitochondrial chaperones and proteases and summarize recent advances in understanding how these proteins are involved in the initiation and progression of heart failure.

Cardiolipin Regulates Mitochondrial Ultrastructure and Function in Mammalian Cells

“…Mitochondria are considered as the powerhouse of the cell, generating the energy required for cellular metabolism through the process of oxidative phosphorylation (OXPHOS) [ 1 ]. These organelles are also involved in many other physiological processes in cells, such as programmed cell death, autophagy, redox signaling, and Ca 2+ homeostasis [ 2 , 3 , 4 ]. Mitochondria contain two membranes, the outer mitochondrial membrane (OMM) and the inner mitochondrial membrane (IMM), and the compartment separated by these two membranes is called the intermembrane space (IMS).…”

Cardiometabolic Changes in Sirtuin1-Heterozygous Mice on High-Fat Diet and Melatonin Supplementation

“…Conversely, HET mice on an HFD with or without melatonin for 16 weeks presented exacerbated lipid peroxidation, mitochondrial oxidative damage, and ER stress indicated by 4HNE, GRP78, and CHOP immunostainings. The persistence of oxidative lipid peroxidation products, like 4HNE, and the activation of mitochondrial/ER chaperones are early factors of cardiomyopathy and ischemic damage, preceding overt heart failure [8,74]. In contrast, the same markers deeply decreased in the heart of WT mice placed on an HFD plus melatonin.…”

“…Given the strict connection between the heart and adipose tissue (AT) in the regulation of metabolism, specific adipose depots must be considered [8]. Indeed, the abdominal visceral white AT (WAT), which forms more than 95% of the adipose mass in humans, is the main target of lipid deposition and energy dissipation during high-calorie intake [9].…”