From mechanisms to therapies: exploiting epigenetic and post-translational modifications of mitochondrial quality control in diabetic kidney disease

Diabetic kidney disease (DKD) is a major and severe microvascular complication of diabetes and one of the primary causes of end-stage renal failure. As the body's largest metabolic organ, the kidneys require a continuous supply of energy to maintain systemic homeostasis and normal metabolic functions. The mitochondrial quality control (MQC) system plays a central role in preserving cellular energy homeostasis by regulating key processes such as mitochondrial biogenesis, dynamics, and mitophagy, which is particularly critical for the highly energy-demanding kidneys. Emerging evidence indicates that epigenetic regulation-including DNA methylation, histone modifications, and non-coding RNA interactions-along with diverse post-translational modifications (PTMs) such as phosphorylation, ubiquitination, methylation, and acetylation, are deeply involved in the fine-tuning of MQC. These regulatory mechanisms significantly contribute to the pathogenesis and progression of DKD. This review systematically summarizes the interplay between MQC, epigenetic regulation, and PTMs, with a focus on how they collectively influence the course and outcome of DKD. Furthermore, it outlines recent advances in therapeutic strategies targeting this regulatory network, aiming to provide novel insights and future research directions for targeted interventions in DKD.