New Publication Led by Dr. Aaron Schimmer
MBP researcher Dr. Aaron Schimmer and has lead a team of collaborators, which includes fellow MBP scientists Dr. Steven Chan, Dr. Mark Minden and Dr. Brian Raught, in the publication of a new Science Translational Medicine article entitled 'The mitochondrial peptidase, neurolysin, regulates respiratory chain supercomplex formation and is necessary for AML viability'.
This research illustrates that targeting mitochondrial supercomplex assembly impairs metabolism and selectively targets leukemia cells.
Abstract
"Neurolysin (NLN) is a zinc metallopeptidase whose mitochondrial function is unclear. We found that NLN was overexpressed in almost half of patients with acute myeloid leukemia (AML), and inhibition of NLN was selectively cytotoxic to AML cells and stem cells while sparing normal hematopoietic cells. Mechanistically, NLN interacted with the mitochondrial respiratory chain. Genetic and chemical inhibition of NLN impaired oxidative metabolism and disrupted the formation of respiratory chain supercomplexes (RCS). Furthermore, NLN interacted with the known RCS regulator, LETM1, and inhibition of NLN disrupted LETM1 complex formation. RCS were increased in patients with AML and positively correlated with NLN expression. These findings demonstrate that inhibiting RCS formation selectively targets AML cells and stem cells and highlights the therapeutic potential of pharmacologically targeting NLN in AML."