A novel role for Bcl2l13 in promoting beige adipocyte biogenesis

Ju, Liping; Chen, Shuqin; Alimujiang, Miriayi; Bai, Ningning; Fang, Qichen; Han, Junfeng; Ma, Xiaojing; Yang, Ying; Jia, Weiping

doi:10.1016/j.bbrc.2018.10.034

Cited by 20 publications

(17 citation statements)

References 24 publications

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“…The mammalian ortholog of the only mitophagy receptor in yeast (atg32) is BCL2L13/BCL-RAMBO, an OMM protein able to bind LC3 and able to induce DRP1-independent mitochondrial fragmentation [80]. Not only BCL2L13 induces Parkin-independent mitophagy [80] and has been associated with NIX/FUNDC1-mediated mitophagy [81], but it is also involved in autophagy-independent mitochondrial quality control [82].…”

Section: Molecular Mechanisms Leading To Mitophagymentioning

confidence: 99%

Mitophagy in Cancer: A Tale of Adaptation

Vara-Pérez

Felipe‐Abrio

Agostinis

2019

Cells

193

134

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In the past years, we have learnt that tumors co-evolve with their microenvironment, and that the active interaction between cancer cells and stromal cells plays a pivotal role in cancer initiation, progression and treatment response. Among the players involved, the pathways regulating mitochondrial functions have been shown to be crucial for both cancer and stromal cells. This is perhaps not surprising, considering that mitochondria in both cancerous and non-cancerous cells are decisive for vital metabolic and bioenergetic functions and to elicit cell death. The central part played by mitochondria also implies the existence of stringent mitochondrial quality control mechanisms, where a specialized autophagy pathway (mitophagy) ensures the selective removal of damaged or dysfunctional mitochondria. Although the molecular underpinnings of mitophagy regulation in mammalian cells remain incomplete, it is becoming clear that mitophagy pathways are intricately linked to the metabolic rewiring of cancer cells to support the high bioenergetic demand of the tumor. In this review, after a brief introduction of the main mitophagy regulators operating in mammalian cells, we discuss emerging cell autonomous roles of mitochondria quality control in cancer onset and progression. We also discuss the relevance of mitophagy in the cellular crosstalk with the tumor microenvironment and in anti-cancer therapy responses.

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Section: Molecular Mechanisms Leading To Mitophagymentioning

confidence: 99%

Mitophagy in Cancer: A Tale of Adaptation

Vara-Pérez

Felipe‐Abrio

Agostinis

2019

Cells

193

134

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“…Furthermore, the incubation of brown preadipocytes with capsaicin, a component of red chili peppers, stimulates brown adipogenesis as well as the expression of UPR genes such as Xbp1 or Chop (Kida et al, 2018). More recently, Ju et al (2018) described the role of a member of the Bcl2 family, Bcl2l13, in the differentiation of brown preadipocytes. Bcl2l13 play a key role in the regulation of mitochondrial dynamics.…”

Section: Mechanisms Involved In Bat Expansionmentioning

confidence: 99%

Mechanisms of Impaired Brown Adipose Tissue Recruitment in Obesity

et al. 2019

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Brown adipose tissue (BAT) dissipates energy to produce heat. Thus, it has the potential to regulate body temperature by thermogenesis. For the last decade, BAT has been in the spotlight due to its rediscovery in adult humans. This is evidenced by over a hundred clinical trials that are currently registered to target BAT as a therapeutic tool in the treatment of metabolic diseases, such as obesity or diabetes. The goal of most of these trials is to activate the BAT thermogenic program via several approaches such as adrenergic stimulation, natriuretic peptides, retinoids, capsinoids, thyroid hormones, or glucocorticoids. However, the impact of BAT activation on total body energy consumption and the potential effect on weight loss is still limited. Other studies have focused on increasing the mass of thermogenic BAT. This can be relevant in obesity, where the activity and abundance of BAT have been shown to be drastically reduced. The aim of this review is to describe pathological processes associated with obesity that may influence the correct differentiation of BAT, such as catecholamine resistance, inflammation, oxidative stress, and endoplasmic reticulum stress. This will shed light on the thermogenic potential of BAT as a therapeutic approach to target obesity-induced metabolic diseases.

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“…The latter in turn has been suggested to be critical for maintaining and controlling "beiging" during thermogenesis (9). Furthermore, a recent report implicated a role for Bcl2l13 in promoting beiging in response to cold and adrenergic activation (10). Despite these initial reports, there is still no clear mechanistic understanding of how Bcl2l13 regulates adipogenesis.…”

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confidence: 99%

The mitophagy receptor Bcl-2–like protein 13 stimulates adipogenesis by regulating mitochondrial oxidative phosphorylation and apoptosis in mice

Fujiwara

Tian

et al. 2019

Journal of Biological Chemistry

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Edited by Jeffrey E. Pessin Metabolic programming of bone marrow stromal cells (BMSCs) could influence the function of progenitor osteoblasts or adipocytes and hence determine skeletal phenotypes. Adipocytes predominantly utilize oxidative phosphorylation, whereas osteoblasts use glycolysis to meet ATP demand. Here, we compared progenitor differentiation from the marrow of two inbred mouse strains, C3H/HeJ (C3H) and C57BL6J (B6). These strains differ in both skeletal mass and bone marrow adiposity. We hypothesized that genetic regulation of metabolic programs controls skeletal stem cell fate. Our experiments identified Bcl-2-like protein 13 (Bcl2l13), a mitochondrial mitophagy receptor, as being critical for adipogenic differentiation. We also found that Bcl2l13 is differentially expressed in the two mouse strains, with C3H adipocyte progenitor differentiation being accompanied by a >2-fold increase in Bcl2l13 levels relative to B6 marrow adipocytes. Bcl2l13 expression also increased during adipogenic differentiation in mouse ear mesenchymal stem cells (eMSCs) and the murine preadipocyte cell line 3T3-L1. The higher Bcl2l13 expression correlated with increased mitochondrial fusion and biogenesis. Importantly, Bcl2l13 knockdown significantly impaired adipocyte differentiation in both 3T3-L1 cells and eMSCs. Mechanistically, Bcl2l13 knockdown reprogrammed cells to rely more on glycolysis to meet ATP demand in the face of impaired oxidative phosphorylation. Bcl2l13 knockdown in eMSCs increased mitophagy. Moreover, Bcl2l13 prevented apoptosis during adipogenesis. Our findings indicate that the mitochondrial receptor Bcl2l13 promotes adipogenesis by increasing oxidative phosphorylation, suppressing apoptosis, and providing mitochondrial quality control through mitophagy. We conclude that genetic programming of metabolism may be important for lineage determination and cell function within the bone marrow.

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A novel role for Bcl2l13 in promoting beige adipocyte biogenesis

Cited by 20 publications

References 24 publications

Mitophagy in Cancer: A Tale of Adaptation

Mitophagy in Cancer: A Tale of Adaptation

Mechanisms of Impaired Brown Adipose Tissue Recruitment in Obesity

The mitophagy receptor Bcl-2–like protein 13 stimulates adipogenesis by regulating mitochondrial oxidative phosphorylation and apoptosis in mice

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