Rescue of mitochondrial import failure by intercellular organellar transfer

• Published in: Nature communications Vol. 15; no. 1; p. 988
• Main Authors: Needs, Hope I., Glover, Emily, Pereira, Gonçalo C., Witt, Alina, Hübner, Wolfgang, Dodding, Mark P., Henley, Jeremy M., Collinson, Ian
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.02.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 101/58; 14; 14/19; 14/35; 631/45/612/1240; 631/80/128; 631/80/642/333/1465; 631/80/86/2366; 82/29; 82/47; 82/80; 82/83; Animals; Bioenergetics; Biological Transport; Cytosol; Cytosol - metabolism; Dihydrofolate reductase; Failure; Humanities and Social Sciences; Imports; Mammalian cells; Mammals - metabolism; Microscopy; Mitochondria; Mitochondria - metabolism; Mitochondrial Proteins - metabolism; Morphology; multidisciplinary; Nanotechnology; Nanotubes; Nervous tissues; Phosphorylation; Protein Transport; Proteins; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-45283-2

Mitochondria are the powerhouses of eukaryotic cells, composed mostly of nuclear-encoded proteins imported from the cytosol. Thus, problems with the import machinery will disrupt their regenerative capacity and the cell’s energy supplies – particularly troublesome for energy-demanding cells of nervous tissue and muscle. Unsurprisingly then, import breakdown is implicated in disease. Here, we explore the consequences of import failure in mammalian cells; wherein, blocking the import machinery impacts mitochondrial ultra-structure and dynamics, but, surprisingly, does not affect import. Our data are consistent with a response involving intercellular mitochondrial transport via tunnelling nanotubes to import healthy mitochondria and jettison those with blocked import sites. These observations support the existence of a widespread mechanism for the rescue of mitochondrial dysfunction. Mitochondrial biogenesis and maintenance relies on protein import from the cytosol. Here, authors show that import failure impacts organelle structure and dynamics. They also identify a rescue mechanism involving intercellular mitochondrial transfer.