Bcl-2-like protein 13 (BCL2L13) (BCL2L13)

Bcl-2-like protein 13 (BCL2L13), also known as Bcl-rambo, is a member of the Bcl-2 family that is uniquely characterized by a C-terminal extension containing tandem repeats and a transmembrane domain that anchors it to the mitochondrial outer membrane. It serves as a critical mammalian mitophagy receptor, acting as a functional homolog of the yeast protein Atg32 to facilitate the selective autophagic degradation of damaged mitochondria by binding to LC3 and GABARAP proteins via its LC3-interacting region (LIR). BCL2L13 exhibits a complex, context-dependent role in cell death; it can promote apoptosis by interacting with the adenine nucleotide translocator (ANT) to trigger mitochondrial permeability transition pore (MPTP) opening, or inhibit it in certain cancers by binding to ceramide synthases (CerS2/6) to prevent Bax-mediated membrane permeabilization. Additionally, it regulates mitochondrial dynamics by promoting mitochondrial fission through the recruitment and activation of the fission protein DNM1L (Drp1). In clinical contexts, BCL2L13 is often overexpressed in glioblastoma and childhood acute lymphoblastic leukemia, where it contributes to tumor survival and therapy resistance, whereas its downregulation is linked to metastasis in lung adenocarcinoma. Although no specific small molecules or biologics targeting BCL2L13 are currently in clinical use, it is considered a promising therapeutic target for treating cancers and neurodegenerative disorders characterized by mitochondrial dysfunction.

Other names

Bcl-ramboMIL1Bcl2-L-13Protein Mil1

Acts as a mitophagy receptor by recruiting LC3/GABARAP to mitochondria via its LIR motif; regulates apoptosis through interactions with the adenine nucleotide translocator (ANT) or inhibition of ceramide synthases (CerS2/6); promotes mitochondrial fission through DNM1L activation.