The role of mitochondrial proteases in leukemic cells and leukemic stem cells
| Autor: | Aaron D. Schimmer, Sara Mirali |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Proteases Acute myelogenous leukemia (AML) medicine.medical_treatment ved/biology.organism_classification_rank.species Respiratory chain Biology acute myelogenous leukemia (AML) 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases medicine cancer Humans Model organism Cell Proliferation Protease ved/biology Myeloid leukemia Cell Biology General Medicine hematologic malignancies medicine.disease hematopoietic stem cells Mitochondria Leukemia Myeloid Acute 030104 developmental biology Mitochondrial respiratory chain Neoplastic Stem Cells Cancer research Stem cell 030217 neurology & neurosurgery Perspectives Peptide Hydrolases Developmental Biology |
| Zdroj: | Stem Cells Translational Medicine |
| ISSN: | 2157-6580 2157-6564 |
| Popis: | The biological function of most mitochondrial proteases has not been well characterized. Moreover, most of the available information on the normal function of these proteases has been derived from studies in model organisms. Recently, the mitochondrial proteases caseinolytic protease P (CLPP) and neurolysin (NLN) have been identified as therapeutic targets in acute myeloid leukemia (AML). Both proteases are overexpressed in approximately 40% of AML patients. Mechanistically, CLPP and NLN maintain the integrity of the mitochondrial respiratory chain: CLPP cleaves defective respiratory chain proteins, while NLN promotes the formation of respiratory chain supercomplexes. In this review, we highlight the functional consequences of inhibiting and activating mitochondrial proteases and discuss their potential as therapeutic targets in AML. The mitochondrial proteases neurolysin (NLN) and caseinolytic protease P (CLPP) have been identified as therapeutic targets in acute myeloid leukemia (AML). Inhibition of NLN by R2 reduces LETM1 complex formation, respiratory chain supercomplex (RCS) assembly, and AML growth. Activation of CLPP by ONC201 or ONC212, as well as inhibition of ClpXP by A2‐32‐01, reduces oxidative metabolism and impairs AML growth. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text