Fig. 2

MiT pathway at the intersection between lysosomes and mitochondria in the context of PD-related genes. MiT transcription factors (MITF, TFE3, TFEB) are activated through the mTOR complex in concert with RagA/B, RagC/D and FLCN/FNIP actions in response to amino acid (AA) availability. Upon dephosphorylation and nuclear translocation, MiT proteins activate transcription of genes involved in lysosomal biogenesis and mitochondrial homeostasis, including PGC-1α and NRF2. Proteins marked in green are examples of proteins implicated in familial forms of PD or carry PD risk alleles that are primarily affecting mitochondria or lysosomal functions. Secondary effects of mutations in those genes impair multiple cellular organelles, including membrane homeostasis and cytoskeleton organization, which reflects on mitochondrial dynamics and autophagy. Metabolites, such as ATP and Ca²⁺ connect mitochondrial and lysosomal functions by indirectly affecting the activation of MiT members through AMPK and Calcineurin (CaN), respectively. Small molecule inhibitors affecting MiT activation are indicated with blunt arrows pointing towards their protein targets. This figure was created using elements from Servier Medical Art, which is licensed under a Creative Commons Attribution 3.0 Unported Generic License (https://creativecommons.org/licenses/by/3.0/)