Mitochondrial biogenesis requires that most of their proteome is imported from the cytosol. This process must be carefully regulated for mitochondrial maintenance, regeneration, and replacement—essential for cellular homeostasis and energy (ATP) supplies. Thus, import failure can be catastrophic for cell and tissue function, particularly where energy demands are high, such as in muscles and the nervous system. Consequentially, mitochondrial import is subject to quality control so that import defective mitochondria are repaired, or where necessary removed. My talk relates to the response to import dysfunction; in the first part to the PINK1 kinase. We show that in addition to its role as a sentinel for import failure and instigator of mitochondrial degradation (mitophagy), PINK1 embarks on an additional unexpected journey. The second part describes another response to import failure: inter-cellular mitochondrial transfer through tunnelling nanotubes (TNTs). We suggest that jettison and recruitment of, respectively, defective or functional mitochondria rescues cells containing import-defective/ failing mitochondria. We speculate that the distinct responses of mitophagy and inter-cellular mitochondrial transfer could be inter related.
Collinson et al. (Sun,) studied this question.