A deeper understanding of how key cellular processes interact is reshaping perspectives on diabetes and its wide-ranging complications. New insights into the relationship between autophagy and ferroptosis are revealing how these fundamental mechanisms influence disease progression and may unlock new possibilities for managing complex metabolic conditions.
Diabetes is widely recognized as a multifactorial metabolic disorder that disrupts normal cellular balance and affects multiple organ systems. At its core, the condition involves intricate changes in how cells maintain stability, process nutrients, and respond to stress. Two processes—autophagy, the cell’s internal recycling system, and ferroptosis, a form of iron-dependent cell death—have emerged as central players in these disruptions.
Autophagy plays a crucial role in preserving cellular health by breaking down damaged components and maintaining energy balance. In contrast, ferroptosis is driven by the accumulation of lipid peroxidation and iron, leading to cell damage and dysfunction. While these processes serve distinct purposes, their interaction creates a dynamic system that can either protect or harm tissues depending on the context.
The impact of this interaction is far-reaching. It influences critical aspects of diabetes, including pancreatic β-cell function, insulin sensitivity, and the development of complications affecting the heart, kidneys, nervous system, and blood vessels. The diagram on page 2 illustrates how prolonged high blood sugar contributes to complications such as diabetic neuropathy, retinopathy, and cardiomyopathy, underscoring the widespread consequences of disrupted cellular processes.
A key feature of this emerging understanding is the recognition that autophagy and ferroptosis are closely interconnected through pathways involving iron metabolism, antioxidant defenses, and lipid regulation. Their interaction forms a tightly controlled system that governs how cells respond to stress and maintain equilibrium. When this balance is disturbed, it can accelerate tissue damage and disease progression.
Importantly, these processes do not act in isolation. They are influenced by a network of regulatory factors that determine whether cells adapt, survive, or undergo damage. This complexity highlights both the challenges and opportunities in addressing diabetes at a cellular level.
As understanding of these mechanisms expands, attention is turning toward how they can be modulated to improve health outcomes. The ability to influence cellular pathways with precision represents a significant shift in thinking, moving beyond symptom management toward targeting the underlying drivers of disease.
These insights position autophagy and ferroptosis as central components in the evolving landscape of diabetes care, offering a more integrated view of how cellular systems contribute to disease and recovery.
# # # # # #
Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
Scopus CiteScore: 10.4 |Impact Factor:14.6
# # # # # #
More information: https://www.keaipublishing.com/en/journals/genes-and-diseases/
Editorial Board: https://www.keaipublishing.com/en/journals/genes-and-diseases/editorial-board/
All issues and articles in press are available online in ScienceDirect (https://www.sciencedirect.com/journal/genes-and-diseases).
Submissions to Genes & Diseases may be made using Editorial Manager (https://www.editorialmanager.com/gendis/default.aspx).
Print ISSN: 2352-4820
eISSN: 2352-3042
CN: 50-1221/R
Contact Us: editor@genesndiseases.cn
X (formerly twitter): @GenesNDiseases (https://x.com/GenesNDiseases)
# # # # # #
Reference
Erlian Xie, Xuerong Wei, Zijun Zheng, Qiuyi Yu, Mengqian Liu, Huihui Zhang, Ziwei Jiang, Yanbin Gao, Lei Yang, Crosstalk between autophagy and ferroptosis in diabetes, Genes & Diseases, Volume 13, Issue 4, 2026, 101936, https://doi.org/10.1016/j.gendis.2025.101936

Funding
National Natural Science Foundation of China 82372526
National Natural Science Foundation of China 82302797
Guangdong Basic and Applied Basic Research Foundation (China) 2023A1515012970
Guangdong Basic and Applied Basic Research Foundation (China) 306217527025).