The diagram shows two cells: one with import-defective mitochondria and one with import-competent mitochondria. The cell with import-defective mitochondria contains accumulating mitochondrial precursors, dysfunctional mitochondria, and a mitochondrial degradation body. The cell with import-competent mitochondria contains healthy mitochondria. Nanotubes connect the two cells, facilitating the transfer of mitochondria. Dysfunctional mitochondria from the import-defective cell are transferred through the nanotube to the import-competent cell, where they undergo degradation via trans-mitophagy. Conversely, healthy mitochondria from the import-competent cell are transferred back to the import-defective cell through another nanotube. The diagram also highlights the presence of a clogger protein, which consists of a mitochondrial targeting sequence (MTS) and a rapidly folding DHFR domain, in the import-defective cell. The process involves signaling mechanisms that are not fully understood.
Ian Collinson and coworkers identified two distinct nanotube types that mediate mitochondrial exchange between cells (1). Healthy cells with import-competent mitochondria were cocultured with import-defective cells expressing a mitochondrial import clogger. These clogger constructs consist of a MTS and a rapidly folding DHFR domain. Clogger-expressing cells transferred compromised fragmented mitochondria to neighboring healthy cells for degradation. Unexpectedly, respiration-active mitochondria were sent back from healthy cells using a second type of nanotubes. In the compromised cells, the freshly received healthy mitochondria are not used for respiration but are degraded in specific structures which the authors termed MDBs. MTS, mitochondrial targeting sequence.