A unique Mitochondrial Quality Control (MQC) mechanism reverses the phagosome maturation arrest caused by Mycobacterium tuberculosis

Here we report a unique crosstalk between mitochondrial quality control (MQC) pathways and the phagosome maturation pathway, which unblocks the PMA and results in the efficient killing of Mtb. Depletion of p62/SQSTM1, a major autophagy adaptor, in human macrophages enhances Mtb killing.

However, depletion of p62/SQSTM1 does not impact mitochondrial quality, despite an apparent block in mitophagy flux. Interestingly, in p62KD cells, MQC is ensured via TOM20+-mitochondria-derived vesicles (MDVs). MDVs, being dependent on RAB7 for maturation, are heavily recruited on Mtb-phagosomes in p62KD cells inadvertently aiding RAB7 recruitment on Mtb-phagosomes thereby releasing the PMA that facilitates efficient lysosomal delivery and killing of Mtb.