Mitochondrial Transfer: From Bench to Bedside.

Area of Science:

• Cardiovascular Biology
• Cellular Biology
• Mitochondrial Medicine

Background:

• Mitochondria were once considered static but are now known to be mobile organelles.
• Intercellular mitochondrial transfer occurs through tunneling nanotubes, extracellular vesicles, and free mitochondria.
• This transfer is crucial for tissue adaptation, repair, and managing cardiovascular, neurological, metabolic, and inflammatory diseases.

Purpose of the Study:

• To summarize the molecular mechanisms of intercellular mitochondrial transfer.
• To discuss the role of mitochondrial transfer in organ function.
• To outline translational strategies for therapeutic applications.

Main Methods:

• Review of molecular machinery governing tunneling nanotube formation, vesicle biogenesis, and mitochondrial release/uptake.
• Analysis of pathways for mitochondrial communication: Rescue by Replenish and Relief by Release.
• Discussion of existing and potential therapeutic interventions.

Main Results:

• Identified key molecular processes facilitating mitochondrial movement between cells.
• Highlighted two primary modes of mitochondrial communication: replenishing healthy mitochondria and releasing damaged ones.
• Proposed four translational strategies including cell-based, cell-free, and pharmacological approaches.

Conclusions:

• Intercellular mitochondrial transfer is a vital process with significant therapeutic potential in cardiovascular medicine.
• Barriers to clinical translation include safety concerns, compatibility issues, and manufacturing challenges.
• Integrating mechanistic insights with bioengineering and regulatory science is crucial for advancing mitochondrial transfer therapies.