Cell-type-targeted mitochondrial transplantation rescues cell degeneration

  • Nature. 2026 May;653(8113):221-231. doi: 10.1038/s41586-026-10391-0.
Temurkhan Ayupov  #  1  2 ,  Verónica Moreno-Juan  #  1 ,  Serena Curtoni  1 ,  Alex Fratzl  1 ,  Upnishad Sharma  3 ,  Susana Posada-Céspedes  1 ,  Ramona Ratiu  1 ,  Rei Morikawa  1 ,  Alexandra Graff Meyer  4 ,  Margherita Pezzoli  5 ,  Glenn Bantug  5 ,  Morgan Chevalier  1 ,  Yanyan Hou  1 ,  Sarah A Nadeau  1 ,  Álvaro Herrero-Navarro  1 ,  Vikram Ayinampudi  1 ,  Elizabeth Kastanaki  1 ,  Natasha Whitehead  1 ,  Rebecca A Siwicki  1 ,  Mariana M Ribeiro  1 ,  Ji Hoon Han  1  2 ,  Annalisa Bucci  1 ,  Christoph Hess  5  6 ,  Simone Picelli  1 ,  Magdalena Renner  1 ,  Daniel J Müller  3 ,  Cameron S Cowan  1 ,  Simon Hansen  1 ,  Botond Roska  7  8
Affiliations
  • 1. Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland.
  • 2. Department of Ophthalmology, University of Basel, Basel, Switzerland.
  • 3. Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
  • 4. Facility for Advanced Imaging and Microscopy, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
  • 5. Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
  • 6. Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK.
  • 7. Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland. [email protected].
  • 8. Department of Ophthalmology, University of Basel, Basel, Switzerland. [email protected].
  • # Contributed equally.
PMID: 41986718 DOI: 10.1038/s41586-026-10391-0
Abstract

A number of currently untreatable diseases, including neurodegenerative disorders, optic nerve atrophy and heart failure, are associated with mitochondrial dysfunction. Transplantation of healthy mitochondria has been proposed as a potential therapeutic strategy1-3. However, the lack of methods to target donor mitochondria to disease-affected cell types limits treatment specificity and efficacy. Here we developed MitoCatch as a system to deliver mitochondria to specific cell types using different types of protein Binders. Donor mitochondria are captured by target cells by cell-surface-displayed monospecific Binders, mitochondrion-displayed monospecific Binders or bispecific Binders linking mitochondria to target cells. Using MitoCatch, we show that donor mitochondria are efficiently internalized, exposed to the cytosol, move, and undergo fusion and fission inside target cells. By engineering Binders with different affinities, we tune the efficiency of mitochondrial delivery. We demonstrate targeted mitochondrial transplantation to retinal cell types, neurons and cardiac, endothelial and immune cells in humans and mice. Transplanted mitochondria promoted the survival of damaged neurons from an individual with optic nerve atrophy in vitro and after neuronal injury in mice in vivo. MitoCatch is a potential strategy to target disease-affected cell types with mitochondria in organs affected by diseases associated with mitochondrial dysfunction.

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