Mitochondrial-Epigenetic Circuits in Heart Failure: From Chromatin Mechanisms to Therapeutic Targets

Heart failure remains a leading cause of global morbidity, and a growing body of 2025–2026 work points to mitochondrial metabolites, NAD⁺, acetyl-CoA, α-ketoglutarate, succinate, as direct regulators of chromatin state and gene transcription in the failing and remodeling heart. This bidirectional mitochondrial-epigenetic axis is now recognized as a distinct mechanistic layer in heart failure and cardiac fibrosis, separate from classical neurohormonal and structural pathways.Despite this momentum, most mechanistic and therapeutic work in the space remains fragmented across separate mitochondrial biology and epigenetics literatures, with few venues connecting the two communities around heart failure specifically. This Research Topic aims to close that gap.We invite original research, reviews, and brief reports addressing:• Mitochondrial metabolites as epigenetic cofactors driving chromatin and non-coding RNA changes in heart failure and cardiac fibrosis;• Interplay between cardiac metabolism, intermediate metabolites (such as TCA cycle and one-carbon pathways), and epigenetic reprogramming across diverse cardiomyopathies and progressive myocardial remodeling;• Single-cell and spatial multi-omic dissection of mitochondrial-epigenetic circuits in HFpEF, HFrEF, and metabolic cardiomyopathy;• Therapeutic strategies targeting mitochondrial-epigenetic crosstalk, including small-molecule and gene-based approaches.By bringing mitochondrial biology and cardiac epigenetics into one collection, this Topic aims to establish a reference point for a mechanistic axis that is rapidly gaining recognition in heart failure research. Topic editors: DeLisa Fairweather, Jun Yu, Jon Sin, Michael Coronado Source: https://www.frontiersin.org/research-topics/85078/mitochondrial-epigenetic-circuits-in-heart-failure-from-chromatin-mechanisms-to-therapeutic-targets