BCL2L13: physiological and pathological meanings
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Cellular and Molecular Life Sciences
REVIEW
BCL2L13: physiological and pathological meanings Fei Meng1,2,3 · Naitong Sun4 · Dongyan Liu1,2,3 · Jia Jia1,2,3 · Jun Xiao5 · Haiming Dai1,3 Received: 23 June 2020 / Revised: 28 October 2020 / Accepted: 3 November 2020 © Springer Nature Switzerland AG 2020
Abstract BCL2L13 is a BCL2-like protein. It has been discovered for two decades, now on the way to be a hotspot of research with its physiological and pathological meanings found in recent years. Start with the pro-apoptotic activity, there have been reported consecutively that BCL2L13 could also induce mitochondrial fragmentation, inhibit cell death and promote mitophagy. Similar to BNIP3, BCL2L13 cannot be indiscriminately categorized into pro- or anti-apoptotic proteins. It anchors in the mitochondrial outer membrane, and expresses in various cells and tissues. This article reviews for the first time that BCL2L13 functions in physiological processes, such as growth and development and energy metabolism, and its dysregulation participating in pathological processes, including cancer, bacterial infection, cardiovascular diseases and degenerative diseases, suggesting its important roles in these events. Keywords BCL-rambo · Autophagy · Apoptosis · Tumor · Cerebrovascular accident · Neurodegenerative disorders
Introduction Regulated cell death (RCD) plays an important role in biological growth and organismal homeostasis, while is commonly dysregulated during aging and diseases [1–3]. RCD relies on tightly structured regulatory network composed of many molecular effectors [4, 5]. B-cell lymphoma 2 (BCL2) family proteins, which are constitutively expressed Fei Meng and Naitong Sun have equally contributed to this work. * Jun Xiao [email protected] * Haiming Dai [email protected] 1
Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health & Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China
2
University of Science and Technology of China, Hefei 230026, China
3
Hefei Cancer Hospital, Chinese Academy of Sciences, 350 Shushanhu Road, Hefei 230031, Anhui, China
4
Department of Hematology, the Third People’s Hospital of Yancheng, Yancheng 224001, China
5
Department of Urology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
in multiple types of cells, regulate the pivotal role of mitochondria mediated cell death pathway [6, 7]. BCL2 was originally identified from the t(14;18) breakpoint in B-cell lymphoma in 1984 [8]. Characterized by the BCL2 homology (BH) domains and grouped by cell death effects, BCL2 family proteins include three sub-families: multi-domain anti-apoptotic members such as BCL2, BCLxL [9], BCLw [10], MCL1 [11] and Caenorhabditis elegans CED-9 [12]; multi-domain pro-apoptotic effector members, e.g., BAX [13] and BAK [14]; BH3-only pro-apoptotic proteins that share only a 15–25 amino acids BH3 motif, like BIK [
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