Biological Properties of the BCL-2 Family Protein BCL-RAMBO, Which Regulates Apoptosis, Mitochondrial Fragmentation, and Mitophagy

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2023 Jan 2

PMID 36589739

Authors

Takao Kataoka

Affiliations

Soon will be listed here.

Abstract

Mitochondria play an essential role in the regulation of cellular stress responses, including cell death. Damaged mitochondria are removed by fission and fusion cycles and mitophagy, which counteract cell death. BCL-2 family proteins possess one to four BCL-2 homology domains and regulate apoptosis signaling at mitochondria. BCL-RAMBO, also known as BCL2-like 13 (BCL2L13), was initially identified as one of the BCL-2 family proteins inducing apoptosis. Mitophagy receptors recruit the ATG8 family proteins MAP1LC3/GABARAP the MAP1LC3-interacting region (LIR) motif to initiate mitophagy. In addition to apoptosis, BCL-RAMBO has recently been identified as a mitophagy receptor that possesses the LIR motif and regulates mitochondrial fragmentation and mitophagy. In the 20 years since its discovery, many important findings on BCL-RAMBO have been increasingly reported. The biological properties of BCL-RAMBO are reviewed herein.

Citing Articles

Mitophagy is required to protect against excessive skeletal muscle atrophy following hindlimb immobilization.

Rahman F, Graham M, Adam A, Juracic E, Tupling A, Quadrilatero J J Biomed Sci. 2025; 32(1):29.

PMID: 39979946 PMC: 11844018. DOI: 10.1186/s12929-025-01118-w.

BCL2L13 at endoplasmic reticulum-mitochondria contact sites regulates calcium homeostasis to maintain skeletal muscle function.

Grepper D, Tabasso C, Zanou N, Aguettaz A, Castro-Sepulveda M, Ziegler D iScience. 2024; 27(8):110510.

PMID: 39175772 PMC: 11340602. DOI: 10.1016/j.isci.2024.110510.

1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit.

Nahalka J Int J Mol Sci. 2024; 25(8).

PMID: 38674024 PMC: 11049929. DOI: 10.3390/ijms25084440.

Molecular mechanism of autophagy and apoptosis in endometriosis: Current understanding and future research directions.

Kobayashi H, Imanaka S, Yoshimoto C, Matsubara S, Shigetomi H Reprod Med Biol. 2024; 23(1):e12577.

PMID: 38645639 PMC: 11031673. DOI: 10.1002/rmb2.12577.

The BCL-2 family protein BCL-RAMBO interacts and cooperates with GRP75 to promote its apoptosis signaling pathway.

Xu J, Hashino T, Tanaka R, Kawaguchi K, Yoshida H, Kataoka T Sci Rep. 2023; 13(1):14041.

PMID: 37640805 PMC: 10462657. DOI: 10.1038/s41598-023-41196-0.

References

Wu W, Tian W, Hu Z, Chen G, Huang L, Li W . ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate mitophagy. EMBO Rep. 2014; 15(5):566-75. PMC: 4210082. DOI: 10.1002/embr.201438501. View

Meng F, Sun N, Liu D, Jia J, Xiao J, Dai H . BCL2L13: physiological and pathological meanings. Cell Mol Life Sci. 2020; 78(6):2419-2428. PMC: 11073179. DOI: 10.1007/s00018-020-03702-9. View

Birgisdottir A, Lamark T, Johansen T . The LIR motif - crucial for selective autophagy. J Cell Sci. 2013; 126(Pt 15):3237-47. DOI: 10.1242/jcs.126128. View

Yuan Y, Zheng Y, Zhang X, Chen Y, Wu X, Wu J . BNIP3L/NIX-mediated mitophagy protects against ischemic brain injury independent of PARK2. Autophagy. 2017; 13(10):1754-1766. PMC: 5640199. DOI: 10.1080/15548627.2017.1357792. View

Kataoka T, Holler N, Micheau O, Martinon F, Tinel A, Hofmann K . Bcl-rambo, a novel Bcl-2 homologue that induces apoptosis via its unique C-terminal extension. J Biol Chem. 2001; 276(22):19548-54. DOI: 10.1074/jbc.M010520200. View

Burte F, Carelli V, Chinnery P, Yu-Wai-Man P . Disturbed mitochondrial dynamics and neurodegenerative disorders. Nat Rev Neurol. 2014; 11(1):11-24. DOI: 10.1038/nrneurol.2014.228. View

Rovira-Llopis S, Banuls C, Diaz-Morales N, Hernandez-Mijares A, Rocha M, Victor V . Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications. Redox Biol. 2017; 11:637-645. PMC: 5284490. DOI: 10.1016/j.redox.2017.01.013. View

Bonora M, Giorgi C, Pinton P . Molecular mechanisms and consequences of mitochondrial permeability transition. Nat Rev Mol Cell Biol. 2021; 23(4):266-285. DOI: 10.1038/s41580-021-00433-y. View

Boumela I, Assou S, Haouzi D, Dechaud H, Ait-Ahmed O, Hamamah S . Developmental regulated expression of anti- and pro-apoptotic BCL-2 family genes during human early embryonic development. Curr Med Chem. 2013; 21(11):1361-9. DOI: 10.2174/09298673113206660278. View

10.

Guarino F, Specchia V, Zapparoli G, Messina A, Aiello R, Bozzetti M . Expression and localization in spermatozoa of the mitochondrial porin isoform 2 in Drosophila melanogaster. Biochem Biophys Res Commun. 2006; 346(3):665-70. DOI: 10.1016/j.bbrc.2006.05.172. View

11.

Chen Q, Shou P, Zheng C, Jiang M, Cao G, Yang Q . Fate decision of mesenchymal stem cells: adipocytes or osteoblasts?. Cell Death Differ. 2016; 23(7):1128-39. PMC: 4946886. DOI: 10.1038/cdd.2015.168. View

12.

Otsu K, Murakawa T, Yamaguchi O . BCL2L13 is a mammalian homolog of the yeast mitophagy receptor Atg32. Autophagy. 2015; 11(10):1932-3. PMC: 4824574. DOI: 10.1080/15548627.2015.1084459. View

13.

Anwar M, Kasper A, Steck A, Schier J . Bongkrekic Acid-a Review of a Lesser-Known Mitochondrial Toxin. J Med Toxicol. 2017; 13(2):173-179. PMC: 5440313. DOI: 10.1007/s13181-016-0577-1. View

14.

Arribat Y, Broskey N, Greggio C, Boutant M, Conde Alonso S, Kulkarni S . Distinct patterns of skeletal muscle mitochondria fusion, fission and mitophagy upon duration of exercise training. Acta Physiol (Oxf). 2018; 225(2):e13179. DOI: 10.1111/apha.13179. View

15.

Strikoudis A, Lazaris C, Trimarchi T, Galvao Neto A, Yang Y, Ntziachristos P . Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a. Nat Cell Biol. 2016; 18(11):1127-1138. PMC: 5083132. DOI: 10.1038/ncb3424. View

16.

Ding H, Chen W, Chen X . Serum miR-96-5p is a novel and non-invasive marker of acute myocardial infarction associated with coronary artery disease. Bioengineered. 2022; 13(2):3930-3943. PMC: 8973839. DOI: 10.1080/21655979.2022.2031392. View

17.

Chouchani E, Kazak L, Spiegelman B . New Advances in Adaptive Thermogenesis: UCP1 and Beyond. Cell Metab. 2018; 29(1):27-37. DOI: 10.1016/j.cmet.2018.11.002. View

18.

Liang M, Ke T, Chen L . Mitochondrial Protein PGAM5 Emerges as a New Regulator in Neurological Diseases. Front Mol Neurosci. 2021; 14:730604. PMC: 8496500. DOI: 10.3389/fnmol.2021.730604. View

19.

Mevel R, Draper J, Lie-A-Ling M, Kouskoff V, Lacaud G . RUNX transcription factors: orchestrators of development. Development. 2019; 146(17). DOI: 10.1242/dev.148296. View

20.

Paul P, Rabaglia M, Wang C, Stapleton D, Leng N, Kendziorski C . Histone chaperone ASF1B promotes human β-cell proliferation via recruitment of histone H3.3. Cell Cycle. 2016; 15(23):3191-3202. PMC: 5176155. DOI: 10.1080/15384101.2016.1241914. View