Inhibition of mitochondrial LonP1 protease by allosteric blockade of ATP binding and hydrolysis via CDDO and its derivatives
Jae Lee, Ashutosh Pandey, Sundararajan Venkatesh, Jayapalraja Thilagavathi, Tadashi Honda, Kamalendra Singh, Carolyn K. Suzuki
Abstract
superfamily of ATPases Associated with diverse cellular Activities, suggesting that CDDO shows selectivity within this family of ATPases. Furthermore, we show that noncytotoxic concentrations of CDDO derivatives in cultured cells inhibited LonP1, but not the 26S proteasome. Taken together, these findings provide insights for future development of LonP1-specific inhibitors with chemotherapeutic potential.
Topics & Concepts
BiologyCell biologyMitochondrionBiochemistryATP hydrolysisBiophysicsATPaseEnzymeATP Synthase and ATPases ResearchMitochondrial Function and PathologyUbiquitin and proteasome pathways