Figure 2. Regulation of mitochondria-lysosome contact site dynamics.

(A) Regulation of contact sites: Mitochondria and lysosomes undergo contact formation and tethering regulated by Rab7 on the lysosomal membrane. Active GTP-bound Rab7 may tether the lysosome to the mitochondria via various Rab7 effector proteins or protein complexes (gray). Subsequently, TBC1D15 (Rab7 GAP) which is recruited to the mitochondria by the outer mitochondrial membrane protein Fis1 drives Rab7 GTP hydrolysis from an active Rab7 GTP-bound state into an inactive Rab7 GDP-bound state at mitochondria-lysosome contacts. This transition from a GTP-bound state to a GDP-bound state leads to GDP-bound Rab7 leaving the lysosomal membrane, resulting in the subsequent untethering of mitochondria-lysosome contacts.

(B) Modulation of organelle dynamics: Mitochondria-lysosome contact sites can simultaneously bidirectionally regulate both mitochondrial and lysosomal network dynamics, including mitochondrial fission events, inter-mitochondrial contact untethering and lysosomal tethering.