Bioinspired Artificial Bioenergetic Organelles: Design Principles, Nanofabrication and Therapeutic Translation

Area of Science:

• Biotechnology
• Nanomedicine
• Synthetic Biology

Background:

• Cellular energy metabolism disruptions are central to many human diseases.
• Conventional therapies often fail to address underlying energetic dysregulation.
• Restoring cellular energy homeostasis is crucial for disease intervention.

Purpose of the Study:

• To review the design, mechanisms, and applications of artificial bioenergetic organelles.
• To highlight their therapeutic potential in various disease models.
• To address translational challenges for clinical application.

Main Methods:

• Engineering bioenergetic organelles from mitochondria and thylakoids.
• Utilizing these organelles as autonomous metabolic modules.
• Investigating their therapeutic effects in preclinical models.

Main Results:

• Artificial bioenergetic organelles restore cellular energy homeostasis by generating ATP, redox equivalents, and oxygen.
• Preclinical studies show therapeutic benefits in conditions like tumor hypoxia, myocardial/neuronal dysfunction, and inflammation.
• These organelles actively remodel pathological microenvironments through metabolic restoration and multi-targeted actions.

Conclusions:

• Bioenergetic organelles represent a transformative therapeutic approach by directly addressing cellular metabolic dysfunction.
• Their biomimetic nature and precise metabolic regulation offer a flexible platform for disease intervention.
• Further research is needed to overcome translational challenges like delivery, immunocompatibility, and safety.