A look at MERCs as UPR^mt regulatory hubs in age-associated heart diseases

With the increase in life expectancy globally, the challenge of dealing with aging becomes more prominent. Aging is a risk factor for several diseases, including cardiovascular disease. Mitochondria, which have long been studied in relation to aging, play a crucial role in maintaining cellular homeostasis. However, there is a limitation in interorganellar communication as organisms age. The unfolded protein response in mitochondria (UPRmt) is activated during stress to maintain mitochondrial homeostasis and prevent the accumulation of damaged mitochondria. This response involves signaling from the mitochondria to the nucleus, leading to transcriptional changes. In the context of aging heart, this review explores the role of mitochondria in terms of function and morphology. It also discusses the impact of UPRmt on cardiac diseases such as heart failure, acute myocardial infarction, and dilated cardiomyopathy. The review also highlights the potential role of mitochondria-endoplasmic reticulum contact sites (MERCs) in modulating UPRmt during aging. Finally, it provides an update on molecules that induce UPRmt activity, potentially benefiting the aging heart with cardiac disease.