Mitokines emerge as potential therapeutic targets for **diabetic nephropathy** by mediating mitochondrial stress responses

Diabetic nephropathy (DN) has become a primary driver of end-stage renal disease (ESRD), yet effective preventive measures to halt its progression remain largely absent. Mitochondria, the cellular energy factories, are crucial for maintaining cell homeostasis. Intriguingly, recent research indicates that when mitochondrial perturbations occur in one tissue, distant tissues can sense and respond through specific mitochondrial stress response pathways, mediated by a group of signaling proteins or peptides known as 'mitokines'.

This comprehensive review systematically analyzed existing literature on 'mitokines' and their involvement in diabetic nephropathy (DN). Researchers identified and cataloged various mitokines, synthesizing current knowledge regarding their mechanisms and observed effects in DN progression. The study explored the potential of these mitochondrial-derived signaling molecules as novel therapeutic targets, summarizing their research progress to date.

The review identified several distinct mitokines implicated in mediating mitochondrial stress responses, which are crucial for maintaining cellular homeostasis across tissues. These proteins and peptides act as intercellular messengers, allowing distal tissues to sense and respond to mitochondrial perturbations originating elsewhere in the body. The synthesis of current research highlights mitokines as promising candidates for therapeutic intervention in diabetic nephropathy (DN), suggesting their involvement in delaying disease progression. Specifically, the paper summarized their known roles in various aspects of DN pathophysiology, including inflammation, oxidative stress, and fibrosis, underscoring their potential to modulate disease pathways and offer novel therapeutic strategies.