Funktionelle Charakterisierung der Rolle von evolutionär konservierten Rho GTPasen bei der Interaktion zwischen Mitochondrien und dem endoplasmischen Retikulum
Zusammenfassung der Projektergebnisse
The viability of cells crucially depends on various cellular compartments that establish unique biochemical and biophysical conditions required for diverse cellular processes. Rather than functioning independently, it is becoming increasingly evident that extensive cross-talk is required between cellular organelles to maintain cellular functions. Such a cross-talk is observed between mitochondria and the endoplasmic reticulum (ER), where phospholipids and Ca2+ are exchanged. Contact between both organelles is mediated at least in part by a protein complex, termed the ERMES complex (ER-mitochondria encounter structure). To understand the functional role of the ERMES complex in these interorganellar contacts, we purified ERMES complexes and identified the Ca2+-binding Miro GTPase Gem1 as an integral component of ERMES. Gem1 regulates the number and size of the ERMES complexes. In vivo, association of Gem1 to ERMES required the first of Gem1's two GTPase domains and the first of its two functional Ca2+-binding domains. In contrast, Gem1's second GTPase domain was required for proper ERMES function in phospholipid exchange. Our results suggest that ERMES is not a passive conduit for interorganellar lipid exchange, but that it can be regulated in response to physiological needs. Furthermore, we provide evidence that the metazoan Gem1 ortholog Miro-1 localizes to sites of ER-mitochondrial contact, suggesting that some of the features ascribed to Gem1 may be evolutionarily conserved.
Projektbezogene Publikationen (Auswahl)
- (2011) The conserved GTPase Gem1 regulates endoplasmic reticulum–mitochondria connections. Proc. Natl. Acad. Sci. U. S. A. 108: 14151–14156
Kornmann B, Osman C & Walter P
