Mitochondrial dysfunction at the crossroad of cardiovascular diseases and cancer

Abstract

A large body of evidence indicates the existence of a complex pathophysiological relationship between cardiovascular diseases and cancer. Mitochondria are crucial organelles whose optimal activity is determined by quality control systems, which regulate critical cellular events, ranging from intermediary metabolism and calcium signaling to mitochondrial dynamics, cell death and mitophagy. Emerging data indicate that impaired mitochondrial quality control drives myocardial dysfunction occurring in several heart diseases, including cardiac hypertrophy, myocardial infarction, ischaemia/reperfusion damage and metabolic cardiomyopathies. On the other hand, diverse human cancers also dysregulate mitochondrial quality control to promote their initiation and progression, suggesting that modulating mitochondrial homeostasis may represent a promising therapeutic strategy both in cardiology and oncology. In this review, first we briefly introduce the physiological mechanisms underlying the mitochondrial quality control system, and then summarize the current understanding about the impact of dysregulated mitochondrial functions in cardiovascular diseases and cancer. We also discuss key mitochondrial mechanisms underlying the increased risk of cardiovascular complications secondary to the main current anticancer strategies, highlighting the potential of strategies aimed at alleviating mitochondrial impairment-related cardiac dysfunction and tumorigenesis. It is hoped that this summary can provide novel insights into precision medicine approaches to reduce cardiovascular and cancer morbidities and mortalities.

Targeting of mitochondrial fission through natural flavanones elicits anti-myeloma activity

“…An increasing number of studies has highlighted cancer-associated defects in mitochondria, which can be harnessed for novel personalized treatments [ 8 ]. Mitochondrial alterations prompt metabolic and phenotypic changes of tumor cells, which have been also implicated in the onset and progression of MM.…”

“…The maintenance of a healthy mitochondrial network, fundamental to support cell energy demand, is strictly dependent on mitochondrial fission and fusion dynamics, a process regulating changes in mitochondrial size and shape, growth and redistribution, as well as intervening in mitochondrial cristae remodeling [ 53 ]. Such a “mitochondrial quality control” system has been found frequently deregulated in pathological conditions, including cardiovascular diseases [ 8 , 54 ], non-alcoholic fatty liver disease [ 55 ], acute kidney injury [ 56 ], neurodegenerative disorders [ 57 , 58 ], diabetes mellitus [ 59 ], skeletal muscle atrophy [ 60 ], and many others.…”

“…These dynamic processes are crucial for the regulation of mitochondrial function, distribution and quality, ensuring that these organelles meet the energy demands of the cell and adapt to various stressors [ 6 , 7 ]. Accordingly, balanced mitochondrial dynamics allows for proper cellular homeostasis, regulating several physiological processes such as energy production, apoptosis, and cellular responses to environmental changes [ 8 ].…”

Comprehensive overview of the role of mitochondrial dysfunction in the pathogenesis of acute kidney ischemia-reperfusion injury: a narrative review

“…Under oxygen-deprived conditions, the activity of complex V is impaired, leading to defects in oxidative phosphorylation. In the IR milieu, excessive ROS production is always accompanied by a reduction in ATP production in the mitochondria [ 18 , 19 ]. However, whether mitochondrial dysfunction is a cause or consequence of excessive mitochondrial ROS production remains unclear.…”

Design, Synthesis, and In Vivo Evaluation of Isosteviol Derivatives as New SIRT3 Activators with Highly Potent Cardioprotective Effects

“…While the intricate mechanisms underlying CVDs remain incompletely understood, mitochondrial dysfunction is recognized as a pivotal factor in their development. Precise modulation of mitochondrial function has been demonstrated to alleviate myocardial injury and preserve cardiac function. − Acetylation, a central player in mitochondrial protein homeostasis, is particularly relevant, with Sirtuin 3 (SIRT3), a NAD+-dependent deacetylase among the seven mammalian sirtuins (SIRT1–7). Notably, SIRT3, alongside SIRT4 and SIRT5, localizes within mitochondria, distinguishing them from counterparts in the nucleus or cytoplasm. − Research indicates that SIRT3, abundantly expressed in healthy hearts, exhibits robust deacetylase activity compared to the weaker activities of SIRT4 and SIRT5. , The primary deacetylation targets of SIRT3 encompass mitochondrial proteins predominantly associated with energy metabolism, redox balance, and mitochondrial dynamics.…”