Fig. 1.

The functional relationship of ML crosstalk in PD pathogenesis. The figure depicts several communication channels between mitochondria and lysosomes. The receptors and connection sites between these organelles are identical, implying that the end organelles operate similarly. Mitophagy, mitochondrial-derived vesicles (MDVs), mitochondrial-derived compartments (MDCs), and membrane contact sites ((MCS) are the key functional interactions between mitochondria and lysosomes. Mitophagy begins with stressed and malfunctioning mitochondria; when the membrane potential of the damaged mitochondria decreases, PINK1 is stabilized, and enzymes are activated (PRKN, LRRK-2, GBA). This further activates the mitochondria digestion into lysosomes, which results in the specific release of MDC and MDV. The release of these chemicals further increases the biogenesis of lysosomes, impairs the replication and some of which lack quality control checkpoints that make them faulty. All these together lead to increased production of the naturally occurring alpha-syn protein. These proteins produce Lewy bodies, which is a confirmatory pathway to PD pathogenesis. (Thelen and Zoncu 2017; Farmacologiche 2018; Ugur et al. 2020)