# Mitochondrial dysfunction in diabetic cardiomyopathy: a review of pathogenic mechanisms and therapeutic strategies

## TL;DR

This review explores how mitochondrial dysfunction contributes to diabetic cardiomyopathy and highlights potential therapeutic strategies to address it.

## Contribution

The paper provides a comprehensive overview of mitochondrial mechanisms in DCM and summarizes emerging mitochondria-targeted therapies.

## Key findings

- Mitochondrial dysfunction is a central driver of diabetic cardiomyopathy through metabolic and oxidative stress pathways.
- Therapies targeting mitochondria, such as antioxidants and gene-based approaches, show promise in treating DCM.
- Future research should focus on multi-targeted interventions and advanced technologies like single-cell transcriptomics.

## 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.