Molecular Signaling to Preserve Mitochondrial Integrity against Ischemic Stress in the Heart: Rescue or Remove Mitochondria in Danger

Abstract

Cardiovascular diseases are one of the leading causes of death and global health problems worldwide, and ischemic heart disease is the most common cause of heart failure (HF). The heart is a high-energy demanding organ, and myocardial energy reserves are limited. Mitochondria are the powerhouses of the cell, but under stress conditions, they become damaged, release necrotic and apoptotic factors, and contribute to cell death. Loss of cardiomyocytes plays a significant role in ischemic heart disease. In response to stress, protective signaling pathways are activated to limit mitochondrial deterioration and protect the heart. To prevent mitochondrial death pathways, damaged mitochondria are removed by mitochondrial autophagy (mitophagy). Mitochondrial quality control mediated by mitophagy is functionally linked to mitochondrial dynamics. This review provides a current understanding of the signaling mechanisms by which the integrity of mitochondria is preserved in the heart against ischemic stress.

Intermittent Hypoxia-Induced Cardiomyocyte Death Is Mediated by HIF-1 Dependent MAM Disruption

“…Indeed, as previously described, MAM plays an important role in Ca 2+ hotspots management and mitochondrial integrity and function [ 57 ]. Preserving mitochondrial function is a key point for keeping the mPTP closed and avoiding apoptosis [ 58 ]. Here, we observed that HIF-1 is responsible for early mPTP opening, suggesting that IH-induced MAM alteration also triggers apoptosis by mPTP early opening.…”

Research progress on the improvement of cardiovascular diseases through the autonomic nervous system regulation of the NLRP3 inflammasome pathway

“…This leads to stress reactions and heightened sympathetic nerve tension due to increased metabolism, ultimately resulting in myocardial cell damage through the mitochondrial pathway ( 59 ). The mitochondrial pathway is a prominent mechanism for myocardial cell death ( 60 ). It promotes inflammatory cells infiltration into myocardial tissue by inducing oxidative stress, loss of growth factors, hypoxia, and triggering NLRP3 activation and DNA damage.…”

Re-evaluation of the cardioprotective effects of cannabinoids against ischemia-reperfusion injury according to the IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) criteria

“…Several recent reviews have highlighted cardioprotective mechanisms that can regulate mitochondrial function, autophagy processes, modulation of energy metabolism, inflammation and apoptosis, and protect from ischemia-reperfusion injury ( Ferdinandy et al, 2023 ). They include activation of PI3K (phosphoinositide-3-kinase (PI3K) and Akt (protein kinase B) ( Deng and Zhou, 2023 ), ERK1/2 (extracellular signal-regulated kinase) ( Kong et al, 2019 ), Pink1/Parkin (PTEN-induced kinase 1 (PINK1) and the E3 ubiquitin ligase Parkin) ( Yu and Miyamoto, 2021 ), AMPK (AMP-activated protein kinase) ( Pakesh et al, 2022 ), p38 MAPK (p38 mitogen-activated protein kinase) ( Ruiz et al, 2018 ) and TGF-β (transforming growth factor-β1)-dependent activation of Smad-dependent cascades ( Humeres et al, 2022 ).…”