Context-Dependent Functional Outcomes of Mitochondrial Transfer: A Donor-Recipient Perspective

Area of Science:

• Cell Biology
• Mitochondrial Biology
• Regenerative Medicine

Background:

• Intercellular mitochondrial transfer is crucial for tissue homeostasis and disease.
• The regulatory network and mechanisms of mitochondrial transfer are not fully understood.

Purpose of the Study:

• To synthesize principal mitochondrial transfer mechanisms (tunneling nanotube- and extracellular vesicle-mediated).
• To categorize functional pairing modes and diversity of mitochondrial transfer.
• To propose key determinants for transfer efficiency and outcomes.

Main Methods:

• Literature review synthesizing current knowledge on mitochondrial transfer.
• Categorization of transfer mechanisms, pairing modes, and influencing factors.
• Framework development for understanding transfer efficiency and functional outcomes.

Main Results:

• Identified tunneling nanotube (TNT) and extracellular vesicle (EV) as principal transfer mechanisms.
• Categorized four pairing modes and diverse functions (metabolic support, repair, stress response).
• Proposed five key determinants: donor quality/capacity, recipient demand/integration, and compatibility.

Conclusions:

• Mitochondrial transfer has dual effects: promoting regeneration and recovery, or driving pathology.
• The proposed framework aids mechanistic studies and clinical translation.
• Highlights therapeutic potential in regenerative medicine, aging, and cancer therapy.