Macrophage mitochondrial fission improves cancer cell phagocytosis induced by therapeutic antibodies and is impaired by glutamine competition

Li, Jiang; Ye, Yingying; Liu, Zhihan; Zhang, Guoyang; Dai, Huiqi; Li, Jiaqian; Zhou, Boxuan; Li, Yihong; Zhao, Qiyi; Huang, Jingying; Feng, Jingwei; Liu, Shu; Ruan, Peigang; Wang, Jinjing; Liu, Jiang; Huang, Min; Liu, Xinwei; Yu, Shubin; Liang, Ziyang; Ma, Liang; Gou, Xiaoxia; Zhang, Guoliang; Chen, Nian; Lu, Yiwen; Di, Can; Xia, Qi‐Dong; Pan, Jiayao; Feng, Ru; Cai, Qingqing; Su, Shicheng

doi:10.1038/s43018-022-00354-5

Cited by 23 publications

(16 citation statements)

References 73 publications

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“…The importance of fission in this efferocytosis response was validated in vivo using myeloid-specific Drp1 -knockout mice. Consistent with these findings, tumour cells resist phagocytosis by human macrophages by inhibiting mitochondrial fission in these cells, and this pathway can be targeted for effective antibody therapy against several malignancies [ 109 ]. In contrast with the pro-phagocytic activity of fission, the fusion-mediating protein MFN2 was also required for phagocytosis, as demonstrated using myeloid-specific Mfn2- knockout mice [ 110 ].…”

Section: Mitochondrial Dynamics and Phagocytosismentioning

confidence: 78%

Mitochondrial dynamics in macrophages: divide to conquer or unite to survive?

Afroz

Raven

Lawrence

et al. 2023

Biochemical Society Transactions

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Mitochondria have long been appreciated as the metabolic hub of cells. Emerging evidence also posits these organelles as hubs for innate immune signalling and activation, particularly in macrophages. Macrophages are front-line cellular defenders against endogenous and exogenous threats in mammals. These cells use an array of receptors and downstream signalling molecules to respond to a diverse range of stimuli, with mitochondrial biology implicated in many of these responses. Mitochondria have the capacity to both divide through mitochondrial fission and coalesce through mitochondrial fusion. Mitochondrial dynamics, the balance between fission and fusion, regulate many cellular functions, including innate immune pathways in macrophages. In these cells, mitochondrial fission has primarily been associated with pro-inflammatory responses and metabolic adaptation, so can be considered as a combative strategy utilised by immune cells. In contrast, mitochondrial fusion has a more protective role in limiting cell death under conditions of nutrient starvation. Hence, fusion can be viewed as a cellular survival strategy. Here we broadly review the role of mitochondria in macrophage functions, with a focus on how regulated mitochondrial dynamics control different functional responses in these cells.

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Section: Mitochondrial Dynamics and Phagocytosismentioning

confidence: 78%

Mitochondrial dynamics in macrophages: divide to conquer or unite to survive?

Afroz

Raven

Lawrence

et al. 2023

Biochemical Society Transactions

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“… 169 Glutamine in tumor microenvironment competitively inhibits mitochondrial fission in macrophages, maintains phase separation of WIP/WASP, and results in clinical antibody resistance. 170 Protein arginine methyltransferases form condensates, and its inhibitor have therapeutic effects in cancer and aging diseases. 171 Moreover, mislocalization of RBPs outside the nucleus such as FUS, TAF15, hnRNP A1, hnRNP A2, and TDP‐43 leads to amyotrophic lateral sclerosis and frontotemporal dementia.…”

Section: Biological Functions Of Biomolecular Condensatesmentioning

confidence: 99%

“…SS18 has oncogenic activity by forming condensates in synovial sarcoma 169 . Glutamine in tumor microenvironment competitively inhibits mitochondrial fission in macrophages, maintains phase separation of WIP/WASP, and results in clinical antibody resistance 170 . Protein arginine methyltransferases form condensates, and its inhibitor have therapeutic effects in cancer and aging diseases 171 .…”

Section: Biological Functions Of Biomolecular Condensatesmentioning

confidence: 99%

“…The condensate NPM1 specifically binds to the PD‐L1 promoter in breast cells and activates PD‐L1 transcription, further inhibiting T cell activity in vitro and in vivo 106,216 . WIP/WASP produces condensates that prevent the protein kinase C‐θ from phosphorylating WIP and reduce efficacy of promising therapeutic antibodies 170 . Furthermore, YTHDF3 increases breast cancer metastasis by enhancing the translation of m6a‐enriched transcripts of ST6GALNAC5, GJA1, and EGFR 104 …”

Section: Biomolecular Condensates Serve As Therapeutic Targets For Di...mentioning

confidence: 99%

“…106,216 WIP/WASP produces condensates that prevent the protein kinase C-θ from phosphorylating WIP and reduce efficacy of promising therapeutic antibodies. 170 Furthermore, YTHDF3 increases breast cancer metastasis by enhancing the translation of m6a-enriched transcripts of ST6GALNAC5, GJA1, and EGFR. 104 Lung cancer or non-small cell lung cancer includes lung adenocarcinoma, lung squamous cell carcinoma, and large cell lung cancer.…”

Section: Condensates Are Therapeutic Targets For a Variety Of Cancersmentioning

confidence: 99%

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Biomolecular condensates: Formation mechanisms, biological functions, and therapeutic targets

Niu

Zhang

et al. 2023

MedComm

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Biomolecular condensates are cellular structures composed of membraneless assemblies comprising proteins or nucleic acids. The formation of these condensates requires components to change from a state of solubility separation from the surrounding environment by undergoing phase transition and condensation. Over the past decade, it has become widely appreciated that biomolecular condensates are ubiquitous in eukaryotic cells and play a vital role in physiological and pathological processes. These condensates may provide promising targets for the clinic research. Recently, a series of pathological and physiological processes have been found associated with the dysfunction of condensates, and a range of targets and methods have been demonstrated to modulate the formation of these condensates. A more extensive description of biomolecular condensates is urgently needed for the development of novel therapies. In this review, we summarized the current understanding of biomolecular condensates and the molecular mechanisms of their formation. Moreover, we reviewed the functions of condensates and therapeutic targets for diseases. We further highlighted the available regulatory targets and methods, discussed the significance and challenges of targeting these condensates. Reviewing the latest developments in biomolecular condensate research could be essential in translating our current knowledge on the use of condensates for clinical therapeutic strategies.

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Mitochondrial fusion–fission dynamics and its involvement in colorectal cancer

Wu,

Xiao,

et al. 2024

Molecular Oncology

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The incidence and mortality rates of colorectal cancer have elevated its status as a significant public health concern. Recent research has elucidated the crucial role of mitochondrial fusion–fission dynamics in the initiation and progression of colorectal cancer. Elevated mitochondrial fission or fusion activity can contribute to the metabolic reprogramming of tumor cells, thereby activating oncogenic pathways that drive cell proliferation, invasion, migration, and drug resistance. Nevertheless, excessive mitochondrial fission can induce apoptosis, whereas moderate mitochondrial fusion can protect cells from oxidative stress. This imbalance in mitochondrial dynamics can exert dual roles as both promoters and inhibitors of colorectal cancer progression. This review provides an in‐depth analysis of the fusion–fission dynamics and the underlying pathological mechanisms in colorectal cancer cells. Additionally, it offers partial insights into the mitochondrial kinetics in colorectal cancer‐associated cells, such as immune and endothelial cells. This review is aimed at identifying key molecular events involved in colorectal cancer progression and highlighting the potential of mitochondrial dynamic proteins as emerging targets for pharmacological intervention.

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Macrophage mitochondrial fission improves cancer cell phagocytosis induced by therapeutic antibodies and is impaired by glutamine competition

Cited by 23 publications

References 73 publications

Mitochondrial dynamics in macrophages: divide to conquer or unite to survive?

Mitochondrial dynamics in macrophages: divide to conquer or unite to survive?

Biomolecular condensates: Formation mechanisms, biological functions, and therapeutic targets

Mitochondrial fusion–fission dynamics and its involvement in colorectal cancer

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