Deficiency of the lysosomal exonuclease PLD3 impacts the degradative route.

PLD3 depletion and exonuclease dysfunction-causing SNPs promote lysosomal impairment and, as such, a congestion of the degradative route. We hypothesize that this could relate to a dysfunctional exonuclease activity of PLD3 in lysosomes. Given the observation of engulfed mitochondria within autophagosomes, the substrates for PLD3 could potentially come from mtDNA.