Nanomaterials regulate cellular functions and influence cell fate through mitophagy

Mitophagy plays a crucial role in maintaining mitochondrial quality control, energy metabolism, redox homeostasis, and cell fate regulation. Its dysregulation is considered a key mechanism underlying the onset and progression of various metabolic disorder- and cell fate abnormality-associated diseases. In recent years, nanomaterials have emerged as ideal tools for modulating mitophagy owing to their designability, targeting capability, and multidimensional regulatory potential. Moreover, moderate activation of mitophagy helps to remove damaged mitochondria, alleviate oxidative stress, and restore metabolic balance, whereas excess or impaired mitophagy may trigger energy crises and lead to cellular injury. However, the bidirectional mechanisms and biosafety issues associated with nanomaterial-mediated mitophagy regulation remain poorly understood. This review highlights recent advances in how nanomaterials regulate cellular functions through mitophagy, focusing on their roles in energy metabolism, oxidative stress, senescence, programmed cell death, and diverse disease models, and summarizes the major signaling pathways involved. This study aimed to provide a theoretical framework for understanding the biological basis of nanomaterial-mediated mitophagy modulation and offer guidance for future nanomedicine design, disease intervention, and safety evaluation.