Pathological Mechanisms and Therapeutic Potential of Mitochondrial Dysfunction in Heart Failure

Figures

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  Fig. 1.. Functional alterations of mitochondria in healthy and HF cardiomyocytes. The left panel depicts healthy cells with normal mitochondrial function, featuring efficient OXPHOS, normal ATP production, and low ROS levels. The right panel shows HF cells with impaired mitochondrial function, suppressed OXPHOS, reduced ATP generation, and elevated ROS accumulation. HF, heart failure; OXPHOS, oxidative phosphorylation; ATP, adenosine triphosphate; ROS, reactive oxygen species; FAD, flavin adenine dinucleotide; FADH2, reduced flavin adenine dinucleotide; NADH, reduced nicotinamide adenine dinucleotide. The Figs. 1,2,3,4 were created with BioRender (https://www.biorender.com).

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  Fig. 2.. Schematic diagram of the synergistic regulatory network of non-coding RNAs on mitochondrial pathways in HF. The lncRNAs, miRNAs, and circRNAs form a hierarchical synergistic regulatory network. lncRNAs initiate upstream regulation, miRNAs perform post-transcriptional fine-tuning, and circRNAs exert stable regulation through ceRNA sponge effects. These three components collaboratively influence mitochondrial energy metabolism, Ca2+ homeostasis, ROS generation, and inflammatory activation, participating in the progression of mitochondrial dysfunction in HF.

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  Fig. 3.. Ferroptosis serves as the central hub. Metabolic remodeling contributes to excessive ROS generation and insufficient ATP production, thereby promoting ferroptosis. Excessive ROS generation further promotes ferroptosis, mtDNA damage and inflammatory activation. These interconnected processes collectively drive the progression of HF.

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  Fig. 4.. Key roles and interactions of metabolic dysregulation, ferroptosis, mtDNA damage, and inflammatory signaling in the pathogenesis and progression of HF.