Relevance of endoplasmic reticulum and mitochondria interactions in age-associated diseases

Oxidative Medicine and Cellular Longevity

et al. 2021

Although the interplay between mitochondria and ER has been identified as a crucial regulator of cellular homeostasis, the pathogenic impact of alterations in mitochondria-ER contact sites (MERCS) during myocardial postischemic reperfusion (I/R) injury remains incompletely understood. Therefore, in our study, we explored the beneficial role played by melatonin in protecting cardiomyocytes against reperfusion injury via stabilizing mitochondria-ER interaction. In vitro exposure of H9C2 rat cardiomyocytes to hypoxia/reoxygenation (H/R) augmented mitochondrial ROS synthesis, suppressed both mitochondrial potential and ATP generation, and increased the mitochondrial permeability transition pore (mPTP) opening rate. Furthermore, H/R exposure upregulated the protein content of CHOP and caspase-12, two markers of ER stress, and enhanced the transcription of main MERCS tethering proteins, namely, Fis1, BAP31, Mfn2, and IP3R. Interestingly, all the above changes could be attenuated or reversed by melatonin treatment. Suggesting that melatonin-induced cardioprotection works through normalization of mitochondria-ER interaction, overexpression of IP3R abolished the protective actions offered by melatonin on mitochondria-ER fitness. These results expand our knowledge on the cardioprotective actions of melatonin during myocardial postischemic reperfusion damage and suggest that novel, more effective treatments for acute myocardial reperfusion injury might be achieved through modulation of mitochondria-ER interaction in cardiac cells.

Section: Introductionmentioning

confidence: 99%

[Retracted] Melatonin Attenuates Cardiac Ischemia‐Reperfusion Injury through Modulation of IP3R‐Mediated Mitochondria‐ER Contact

Liu

Oxidative Medicine and Cellular Longevity

et al. 2021

“…Decreased numbers of MAMs in senescent cells lead to a decrease in the ability of mitochondria and endoplasmic reticulum to coordinately regulate [75]. Aging-associated reduced ER content may lead to reduced MAMs, which can lead to decreased mitophagy and trigger mitochondrial dysfunction [75,76]. Alterations in the mitochondrial-ER calcium flux can also affect aging in mice.…”

Section: Aging-and Exercise-associated Alterations In Mamsmentioning

confidence: 99%

Impact of Exercise and Aging on Mitochondrial Homeostasis in Skeletal Muscle: Roles of ROS and Epigenetics

et al. 2022

Cells

Aging causes degenerative changes such as epigenetic changes and mitochondrial dysfunction in skeletal muscle. Exercise can upregulate muscle mitochondrial homeostasis and enhance antioxidant capacity and represents an effective treatment to prevent muscle aging. Epigenetic changes such as DNA methylation, histone posttranslational modifications, and microRNA expression are involved in the regulation of exercise-induced adaptive changes in muscle mitochondria. Reactive oxygen species (ROS) play an important role in signaling molecules in exercise-induced muscle mitochondrial health benefits, and strong evidence emphasizes that exercise-induced ROS can regulate gene expression via epigenetic mechanisms. The majority of mitochondrial proteins are imported into mitochondria from the cytosol, so mitochondrial homeostasis is regulated by nuclear epigenetic mechanisms. Exercise can reverse aging-induced changes in myokine expression by modulating epigenetic mechanisms. In this review, we provide an overview of the role of exercise-generated ROS in the regulation of mitochondrial homeostasis mediated by epigenetic mechanisms. In addition, the potential epigenetic mechanisms involved in exercise-induced myokine expression are reviewed.

“…The adaptor protein p66Shc located in the MAMs is considered as a sensor of oxidative stress-induced apoptosis ( Mishra et al, 2019 ). Experiments with a p66Shc knockout mouse showed that a reduced number of atherosclerotic plaques formed ( Napoli et al, 2003 ; Gil-Hernández and Silva-Palacios, 2020 ).…”

Section: The Critical Role Of Endoplasmic Reticulum-mitochondria Contacts In Remodeling and Cardiovascular Remodeling-associated Diseasesmentioning

confidence: 99%

Endoplasmic Reticulum-Mitochondria Contacts: A Potential Therapy Target for Cardiovascular Remodeling-Associated Diseases

Zhang

Wen

et al. 2021

Front. Cell Dev. Biol.

Cardiovascular remodeling occurs in cardiomyocytes, collagen meshes, and vascular beds in the progress of cardiac insufficiency caused by a variety of cardiac diseases such as chronic ischemic heart disease, chronic overload heart disease, myocarditis, and myocardial infarction. The morphological changes that occur as a result of remodeling are the critical pathological basis for the occurrence and development of serious diseases and also determine morbidity and mortality. Therefore, the inhibition of remodeling is an important approach to prevent and treat heart failure and other related diseases. The endoplasmic reticulum (ER) and mitochondria are tightly linked by ER-mitochondria contacts (ERMCs). ERMCs play a vital role in different signaling pathways and provide a satisfactory structural platform for the ER and mitochondria to interact and maintain the normal function of cells, mainly by involving various cellular life processes such as lipid metabolism, calcium homeostasis, mitochondrial function, ER stress, and autophagy. Studies have shown that abnormal ERMCs may promote the occurrence and development of remodeling and participate in the formation of a variety of cardiovascular remodeling-associated diseases. This review focuses on the structure and function of the ERMCs, and the potential mechanism of ERMCs involved in cardiovascular remodeling, indicating that ERMCs may be a potential target for new therapeutic strategies against cardiovascular remodeling-induced diseases.