Intercellular Mitochondria Transfer in Lung Diseases: New Mechanisms, Risks, Therapeutic Boundaries

Abstract

Significance: Intercellular mitochondrial transfer (MT) is increasingly recognized as more than a mechanism of bioenergetic rescue. By modulating mitochondrial quality control, redox homeostasis, immune-cell metabolism, and cell-death susceptibility, MT may influence disease progression and therapeutic response in lung diseases. Recent Advances: Studies have shown that engineered enhancement of mitochondrial biogenesis and transfer can restore mitochondrial homeostasis and attenuate pulmonary fibrosis. In cancer, mitochondrial acquisition can enhance metastatic fitness, redox buffering, and immune escape, whereas directed MT to T cells can improve T-cell antitumor activity. Emerging evidence further links MT to the regulation of oxidative stress, ferroptosis sensitivity, and redox-dependent immune remodeling within the tumor microenvironment. Critical Issues: The biological consequences of MT remain highly context dependent. Transfer efficiency, persistence of transferred mitochondria, cargo quality, and long-term integration into recipient-cell mitochondrial networks remain insufficiently characterized. The same process may promote tissue repair in the injured lung while conferring metabolic advantages on malignant cells, thereby defining important therapeutic and safety boundaries. Future Directions: Future studies should clarify how mitochondrial cargo quality, recipient-cell identity, and microenvironmental state shape MT outcomes. Improved methods for tracking mitochondrial fate and assessing long-term functional integration will be essential for translating MT-based strategies into safe and effective clinical therapies. Antioxid. Redox Signal. 45, 879–907.