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With the increasingly severe situation of obesity and population aging, there is growing concern about sarcopenia obesity (SO). SO refers to the coexistence of obesity and sarcopenia, which imposes a heavier burden on individuals and society compared to obesity or sarcopenia alone. Therefore, comprehending the pathogenesis of SO and implementing effective clinical interventions are vital for its prevention and treatment. This review uses a comprehensive literature search and analysis of PubMed, Web of Science, and CNKI databases, with search terms including \"Sarcopenic obesity\", \"exercise\", \"cytokines\", \"inflammation\", \"mitochondrial quality control\", and \"microRNA\", covering relevant studies published up to July 2024. The results indicate that the pathogenesis of SO is complex, involving mechanisms like age-related changes in body composition, hormonal alterations, inflammation, mitochondrial dysfunction, and genetic and epigenetic factors. Regarding exercise interventions for SO, aerobic exercise can reduce fat mass, resistance exercise can increase skeletal muscle mass and strength, and combined exercise can achieve both, making it the optimal intervention for SO. The potential mechanisms by which exercise may prevent and treat SO include regulating cytokine secretion, inhibiting inflammatory pathways, improving mitochondrial quality, and mediating microRNA expression. This review emphasizes the effectiveness of exercise interventions in mitigating sarcopenic obesity through comprehensive analysis of its multifactorial pathogenesis and the mechanistic insights into exercise's therapeutic effects. Understanding these mechanisms informs targeted therapeutic strategies aimed at alleviating the societal and individual burdens associated with SO.

Diabetic kidney disease (DKD) is the predominant complication of diabetes mellitus (DM) and the leading cause of chronic kidney disease and end-stage renal disease worldwide, which are major risk factors for death. The pathogenesis of DKD is very complicated, including inflammation, autophagy impairment, oxidative stress, and so on. Recently, accumulating evidence suggests that the loss of mitochondrial quality control exerts critical roles in the progression of DKD. Mitochondria are essential for eukaryotic cell viability but are extremely vulnerable to damage. The mechanisms of mitochondrial quality control act at the molecular level and the organelle level, including mitochondrial dynamics (fusion and fission), mitophagy, mitochondrial biogenesis, and mitochondrial protein quality control. In this review, we summarize current knowledge of the role of disturbances in mitochondrial quality control in the pathogenesis of DKD and provide potential insights to explore how to delay the onset and development of DKD.

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by impaired cognitive function due to progressive loss of neurons in the brain. Under the microscope, neuronal accumulation of abnormal tau proteins and amyloid plaques are two pathological hallmarks in affected brain regions. Although the detailed mechanism of the pathogenesis of AD is still elusive, a large body of evidence suggests that damaged mitochondria likely play fundamental roles in the pathogenesis of AD. It is believed that a healthy pool of mitochondria not only supports neuronal activity by providing enough energy supply and other related mitochondrial functions to neurons, but also guards neurons by minimizing mitochondrial related oxidative damage. In this regard, exploration of the multitude of mitochondrial mechanisms altered in the pathogenesis of AD constitutes novel promising therapeutic targets for the disease. In this review, we will summarize recent progress that underscores the essential role of mitochondria dysfunction in the pathogenesis of AD and discuss mechanisms underlying mitochondrial dysfunction with a focus on the loss of mitochondrial structural and functional integrity in AD including mitochondrial biogenesis and dynamics, axonal transport, ER-mitochondria interaction, mitophagy and mitochondrial proteostasis.

The progressive decline of cell function and integrity, manifesting clinically as increased vulnerability to adverse outcomes and death, is core to biological aging. Mitochondrial dysfunction, oxidative stress, altered intercellular communication (including chronic low-grade inflammation), genomic instability, telomere attrition, loss of proteostasis, altered nutrient sensing, epigenetic alterations, and stem cell exhaustion have been proposed as hallmarks of aging. These “aging pillars” are not mutually exclusive, making the matter intricate and leaving numerous unanswered questions. The characterization of circulating extracellular vesicles (EVs) has recently allowed specific secretory phenotypes associated with aging to be identified. As such, EVs may serve as novel biomarkers for capturing the complexity of aging. Besides the mitochondrial–lysosomal axis, EV trafficking has been proposed as an additional layer in mitochondrial quality control. Indeed, disruption of the mitochondrial–lysosomal axis coupled with abnormal EV secretion may play a role in the pathogenesis of aging and several disease conditions. Here, we discuss (1) the mechanisms of EV generation; (2) the relationship between the mitochondrial–lysosomal axis and EV trafficking in the setting of mitochondrial quality control; and (3) the prospect of using EVs as aging biomarkers and as delivery systems for therapeutics against age-related conditions.

Ischemic cardiomyopathy (ICM) is a special type of coronary heart disease or an advanced stage of the disease, which is related to the pathological mechanism of primary dilated cardiomyopathy. Ischemic cardiomyopathy mainly occurs in the long-term myocardial ischemia, resulting in diffuse myocardial fibrosis. This in turn affects the cardiac ejection function, resulting in a significant impact on myocardial systolic and diastolic function, resulting in a decrease in the cardiac ejection fraction. The pathogenesis of ICM is closely related to coronary heart disease. Mainly due to coronary atherosclerosis caused by coronary stenosis or vascular occlusion, causing vascular inflammatory lesions and thrombosis. As the disease progresses, it leads to long-term myocardial ischemia and eventually ICM. The pathological mechanism is mainly related to the mechanisms of inflammation, myocardial hypertrophy, fibrosis and vascular remodeling. Mitochondria are organelles with a double-membrane structure, so the composition of the mitochondrial outer compartment is basically similar to that of the cytoplasm. When ischemia-reperfusion induces a large influx of calcium into the cell, the concentration of calcium ions in the mitochondrial outer compartment also increases. The subsequent opening of the membrane permeability transition pore in the inner mitochondrial membrane and the resulting calcium overload induces the homeostasis of cardiomyocytes and activates the mitochondrial pathway of apoptosis. Mitochondrial Quality Control (MQC), as an important mechanism for regulating mitochondrial function in cardiomyocytes, affects the morphological structure/function and lifespan of mitochondria. In this review, we discuss the role of MQC (including mitophagy, mitochondrial dynamics, and mitochondrial biosynthesis) in the pathogenesis of ICM and provide important evidence for targeting MQC for ICM.

Among the complex determinants of aging, mitochondrial dysfunction has been in the spotlight for a long time. As the hub for many cellular functions, the maintenance of an adequate pool of functional mitochondria is crucial for tissue homeostasis. Their unique role in energy supply makes these organelles essential, especially in those tissues strictly dependent on oxidative metabolism. Mitochondrial quality control (MQC) is ensured by pathways related to protein folding and degradation as well as by processes involving the entire organelle, such as biogenesis, dynamics, and mitophagy. Dysfunctional MQC, oxidative stress and inflammation are hallmarks of senescence and chronic degenerative diseases. One of the consequences of age-related failing MQC and oxidative stress is the release of mitochondria-derived damage-associated molecular patterns (DAMPs). Through their bacterial ancestry, these molecules contribute to mounting an inflammatory response by interacting with receptors similar to those involved in pathogen-associated responses. Mitochondrial DAMPs, especially cell-free mitochondrial DNA, have recently become the subject of intensive research because of their possible involvement in conditions associated with inflammation, such as aging and degenerative diseases. Here, we review the contribution of mitochondrial DAMPs to inflammation and discuss some of the mechanisms at the basis of their generation.

Mitochondria with structural and functional integrity are essential for maintaining mitochondrial function and cardiac homeostasis. It is involved in the pathogenesis of many diseases. Peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1 α ), acted as a transcriptional cofactor, is abundant in the heart, which modulates mitochondrial biogenesis and mitochondrial dynamics and mitophagy to sustain a steady-state of mitochondria. Cumulative evidence suggests that dysregulation of PGC-1 α is closely related to the onset and progression of heart failure. PGC-1 α deficient-mice can lead to worse cardiac function under pressure overload compared to sham. Here, this review mainly focuses on what is known about its regulation in mitochondrial functions, as well as its crucial role in heart failure.

Endothelial cells (ECs) constitute the innermost layer in all blood vessels to maintain the structural integrity and microcirculation function for coronary microvasculature. Impaired endothelial function is demonstrated in various cardiovascular diseases including myocardial infarction (MI), which is featured by reduced myocardial blood flow as a result of epicardial coronary obstruction, thrombogenesis, and inflammation. In this context, understanding the cellular and molecular mechanisms governing the function of coronary ECs is essential for the early diagnosis and optimal treatment of MI. Although ECs contain relatively fewer mitochondria compared with cardiomyocytes, they function as key sensors of environmental and cellular stress, in the regulation of EC viability, structural integrity and function. Mitochondrial quality control (MQC) machineries respond to a broad array of stress stimuli to regulate fission, fusion, mitophagy and biogenesis in mitochondria. Impaired MQC is a cardinal feature of EC injury and dysfunction. Hence, medications modulating MQC mechanisms are considered as promising novel therapeutic options in MI. Here in this review, we provide updated insights into the key role of MQC mechanisms in coronary ECs and microvascular dysfunction in MI. We also discussed the option of MQC as a novel therapeutic target to delay, reverse or repair coronary microvascular damage in MI. Contemporary available MQC-targeted therapies with potential clinical benefits to alleviate coronary microvascular injury during MI are also summarized.

Mitochondrial function is maintained by several strictly coordinated mechanisms, collectively termed mitochondrial quality control mechanisms, including fusion and fission, degradation, and biogenesis. As the primary source of energy in cardiomyocytes, mitochondria are the central organelle for maintaining cardiac function. Since adult cardiomyocytes in humans rarely divide, the number of dysfunctional mitochondria cannot easily be diluted through cell division. Thus, efficient degradation of dysfunctional mitochondria is crucial to maintaining cellular function. Mitophagy, a mitochondria specific form of autophagy, is a major mechanism by which damaged or unnecessary mitochondria are targeted and eliminated. Mitophagy is active in cardiomyocytes at baseline and in response to stress, and plays an essential role in maintaining the quality of mitochondria in cardiomyocytes. Mitophagy is mediated through multiple mechanisms in the heart, and each of these mechanisms can partially compensate for the loss of another mechanism. However, insufficient levels of mitophagy eventually lead to mitochondrial dysfunction and the development of heart failure. In this review, we discuss the molecular mechanisms of mitophagy in the heart and the role of mitophagy in cardiac pathophysiology, with the focus on recent findings in the field.

Ischemic stroke is one of the leading causes of death and also a major cause of adult disability worldwide. Revascularization via reperfusion therapy is currently a standard clinical procedure for patients with ischemic stroke. Although the restoration of blood flow (reperfusion) is critical for the salvage of ischemic tissue, reperfusion can also, paradoxically, exacerbate neuronal damage through a series of cellular alterations. Among the various theories postulated for ischemia/reperfusion (I/R) injury, including the burst generation of reactive oxygen species (ROS), activation of autophagy, and release of apoptotic factors, mitochondrial dysfunction has been proposed to play an essential role in mediating these pathophysiological processes. Therefore, strict regulation of the quality and quantity of mitochondria via mitochondrial quality control is of great importance to avoid the pathological effects of impaired mitochondria on neurons. Furthermore, timely elimination of dysfunctional mitochondria via mitophagy is also crucial to maintain a healthy mitochondrial network, whereas intensive or excessive mitophagy could exacerbate cerebral I/R injury. This review will provide a comprehensive overview of the effect of mitochondrial quality control on cerebral I/R injury and introduce recent advances in the understanding of the possible signaling pathways of mitophagy and potential factors responsible for the double-edged roles of mitophagy in the pathological processes of cerebral I/R injury.