MOF-Coated Mitochondria Retain ATP Output in Vitro, Opening Path to Engineered Transplantation

The team at IRCCS Fondazione Istituto Neurologico Carlo Besta and Politecnico di Milano applied thin MOF layers directly onto mouse and human mitochondria via controlled solution-phase growth. Respirometry assays showed oxygen consumption rates and ATP synthesis remained statistically indistinguishable from uncoated controls across multiple substrate conditions. This in-vitro proof-of-concept addresses the long-standing barrier that prior surface modifications often collapsed membrane potential or blocked electron transport chain complexes.

Mitochondrial transplantation trials for MELAS and other primary mitochondrial disorders have so far relied on naked organelles with poor uptake and rapid clearance. Customizable MOF shells could add targeting ligands or protective barriers while the 2025 Nobel recognition of MOF tunability supplies a ready chemical toolkit. The work bridges materials chemistry and neurogenetics but remains at the isolated-organelle stage.

Next steps require whole-cell uptake studies and in-vivo transplantation models to test whether coated mitochondria show improved engraftment or altered immunogenicity. Parallel efforts should quantify any long-term effects on cristae architecture or ROS signaling. Only then can the approach move toward GMP-grade mitochondrial therapeutics.

Key limitation is the absence of functional data inside living cells or animals; scaling the coating uniformly across heterogeneous mitochondrial populations also remains untested.