Advances in Mitochondrial Dysfunction and Its Role in Cardiovascular Diseases

Figure 1. Mitochondrial quality control through dynamics and mitophagy. Mitochondrial integrity is maintained through coordinated fission and fusion, as well as mitophagy. Damaged fragments are segregated via Drp1-mediated fission and removed by autophagy. Mitochondrial fusion mediated by Mfn1/2 and OPA1 supports functional complementation. PGC-1α regulates mitochondrial biogenesis. Collectively, these processes maintain mitochondrial homeostasis. Abbreviations: AMPK, Adenosine 5′-monophosphate-activated Protein Kinase;Drp1, Dynamin-Related Protein 1; ER, endoplasmic reticulum; Mfn1/2, Mitofusins 1/2; OPA1, Optic Atrophy 1; PGC-1α, Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α; PINK, PTEN-Induced Kinase.

Figure 2. Mitochondrial dysfunction in atherosclerosis. Foam cell formation is stimulated by ox-LDL-induced endothelial activation and monocyte recruitment. Mitochondrial dysfunction in macrophages increases ROS production and inflammatory signaling, disrupts lipid metabolism, and accelerates necrotic core formation, thereby exacerbating plaque progression. Abbreviations: EC, endothelial cells; LDL, low-density lipoprotein; SMC, smooth muscle cells; VCAM-1, vascular cell adhesion molecule 1.

Figure 3. Mitochondrial dysfunction in myocardial IRI. Reperfusion triggers an intracellular Na+/Ca2+ overload and excessive mitochondrial ROS production. The opening of the mPTP exacerbates damage, facilitating further ROS release and immune cell infiltration via DAMPs, thereby amplifying IRI. Abbreviations: cGAS, cyclic GMP–AMP syntheses; MMP, mitochondrial membrane potential; mPTP, mitochondrial permeability transition pore; PRR, pattern recognition receptor; STING, stimulator of interferon genes.

Figure 4. Mitochondrial dysfunction in HF. Dysfunctional mitochondria contribute to HF by impairing ATP production and elevating ROS levels, which initiate a cascade of cellular damage, inflammation, and progressive cardiac dysfunction. Abbreviations: ATP, adenosine triphosphate; OXPHOS, oxidative phosphorylation. Upward arrows indicate activation; downward arrows indicate inhibition.

Figure 5. Mechanisms of mitochondrial dysfunction and current therapeutic strategies. A schematic overview illustrating the key mechanisms contributing to mitochondrial dysfunction, including impaired OXPHOS, ROS overproduction, mtDNA damage, and disrupted mitochondrial dynamics, as well as targeted therapeutic interventions such as antioxidants, metabolic modulators, and MQC enhancers. Abbreviations: ATP, adenosine triphosphate; mPTP, mitochondrial permeability transition pore; MitoQ, mitoquinone; mPTP, mitochondrial permeability transition pore; MQC, mitochondrial quality control.