REVIEW article
Front. Cardiovasc. Med.
Sec. Cardiovascular Metabolism
Mitochondrial dysfunction in diabetic cardiomyopathy: a review of pathogenic mechanisms and therapeutic strategies
Yulian Huang
Qiao Ma
Wang Wei
Shanjun Huang
Jianqiang Zhao
Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Abstract
Diabetic cardiomyopathy (DCM) presents a significant clinical challenge, independently contributing to heart failure morbidity and mortality in patients with diabetes mellitus. Although advancements in glycemic control and cardiovascular therapies have been made, effective strategies specifically addressing DCM remain limited, highlighting the urgent need to clarify its underlying pathogenesis. Recent research has increasingly recognized mitochondrial dysfunction as a central driver of DCM, linking metabolic derangements, oxidative stress, inflammation, and programmed cell death into a complex pathological network. This review critically examines recent experimental and clinical findings to delineate the multidimensional mechanisms by which mitochondrial impairment propels DCM progression. We specifically explore alterations in energy metabolism, excessive reactive oxygen species (ROS) production, inflammasome activation, and dysregulation of apoptotic and ferroptotic pathways. Additionally, we summarize the latest advances in mitochondria-targeted therapeutic strategies, including small molecule antioxidants, metabolic modulators, gene-based therapies, stem cell-derived exosomes, and lifestyle interventions aimed at restoring mitochondrial health. Finally, we briefly highlight future research directions, emphasizing the potential of multi-targeted interventions and emerging technologies such as single-cell transcriptomics to deepen mechanistic insights. A comprehensive understanding of mitochondrial-centered pathways may offer promising avenues for innovative therapies and improved clinical outcomes in DCM.
Summary
Keywords
Cell Death, Diabetic cardiomyopathy, metabolic remodeling, Mitochondrial dysfunction, Oxidative Stress, Targeted interventions
Received
05 January 2026
Accepted
19 February 2026
Copyright
© 2026 Huang, Ma, Wei, Huang and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Jianqiang Zhao
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.