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ATP-dependent mitochondrial metalloprotease YME1L1 (YME1L) is a member of the AAA+ (ATPases associated with diverse cellular activities) family located in the inner mitochondrial membrane (UniProt Q96TA2). It is essential for mitochondrial protein quality control, degrading misfolded proteins and regulating mitochondrial morphology by cleaving the dynamin-like GTPase OPA1 (PubMed: 21930788). In oncology, YME1L1 is frequently upregulated, particularly in pancreatic and breast cancers, where it facilitates metabolic rewiring and protects against proteotoxic stress (PubMed: 31164702). Research into targeting YME1L1 mRNA using siRNA or antisense oligonucleotides has demonstrated potential in suppressing tumor growth by inducing mitochondrial dysfunction and apoptosis (PubMed: 34108481). However, because YME1L1 is vital for normal mitochondrial maintenance, therapeutic strategies must carefully balance efficacy against potential toxicities such as neurodegeneration or cardiomyopathy (PubMed: 27453337). Loss-of-function mutations in the YME1L1 gene are associated with infantile-onset mitochondrial encephalopathy and optic atrophy (PubMed: 27453337).
Proteolytic degradation of mitochondrial substrates and regulation of OPA1-mediated mitochondrial fusion
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