MCOLN/TRPML channels in the regulation of MTORC1 and autophagy
Autophagy. 2024 Jan 5:1-2. doi: 10.1080/15548627.2023.2300922. Online ahead of print.ABSTRACTMCOLN1 and MCOLN3 are two Ca2+ release channels residing in the endolysosomal membrane. They are activated by phosphatidylinositol (PtdIns)-3-phosphate (PtdIns3P) and/or PtdIns(3,5)P2. Their activities are also regulated by lumenal pH, with low pH enhancing that of MCOLN1 and high pH increasing that of MCOLN3. Recent studies further suggest that upon starvation, both MCOLN1 and MCOLN3 are activated by a reduction in MTORC1 activity; their activation in turn regulates MTORC1 activity to facilitate macroautophagic/autophagic flux. On...
Source: Autophagy - January 5, 2024 Category: Cytology Authors: Peng Huang Rose Yang Dong Pingping Wang Mengnan Xu Xue Sun Xian-Ping Dong Source Type: research
MCOLN/TRPML channels in the regulation of MTORC1 and autophagy
Autophagy. 2024 Jan 5:1-2. doi: 10.1080/15548627.2023.2300922. Online ahead of print.ABSTRACTMCOLN1 and MCOLN3 are two Ca2+ release channels residing in the endolysosomal membrane. They are activated by phosphatidylinositol (PtdIns)-3-phosphate (PtdIns3P) and/or PtdIns(3,5)P2. Their activities are also regulated by lumenal pH, with low pH enhancing that of MCOLN1 and high pH increasing that of MCOLN3. Recent studies further suggest that upon starvation, both MCOLN1 and MCOLN3 are activated by a reduction in MTORC1 activity; their activation in turn regulates MTORC1 activity to facilitate macroautophagic/autophagic flux. On...
Source: Autophagy - January 5, 2024 Category: Cytology Authors: Peng Huang Rose Yang Dong Pingping Wang Mengnan Xu Xue Sun Xian-Ping Dong Source Type: research
MCOLN/TRPML channels in the regulation of MTORC1 and autophagy
Autophagy. 2024 Jan 5:1-2. doi: 10.1080/15548627.2023.2300922. Online ahead of print.ABSTRACTMCOLN1 and MCOLN3 are two Ca2+ release channels residing in the endolysosomal membrane. They are activated by phosphatidylinositol (PtdIns)-3-phosphate (PtdIns3P) and/or PtdIns(3,5)P2. Their activities are also regulated by lumenal pH, with low pH enhancing that of MCOLN1 and high pH increasing that of MCOLN3. Recent studies further suggest that upon starvation, both MCOLN1 and MCOLN3 are activated by a reduction in MTORC1 activity; their activation in turn regulates MTORC1 activity to facilitate macroautophagic/autophagic flux. On...
Source: Autophagy - January 5, 2024 Category: Cytology Authors: Peng Huang Rose Yang Dong Pingping Wang Mengnan Xu Xue Sun Xian-Ping Dong Source Type: research
MCOLN/TRPML channels in the regulation of MTORC1 and autophagy
Autophagy. 2024 Jan 5:1-2. doi: 10.1080/15548627.2023.2300922. Online ahead of print.ABSTRACTMCOLN1 and MCOLN3 are two Ca2+ release channels residing in the endolysosomal membrane. They are activated by phosphatidylinositol (PtdIns)-3-phosphate (PtdIns3P) and/or PtdIns(3,5)P2. Their activities are also regulated by lumenal pH, with low pH enhancing that of MCOLN1 and high pH increasing that of MCOLN3. Recent studies further suggest that upon starvation, both MCOLN1 and MCOLN3 are activated by a reduction in MTORC1 activity; their activation in turn regulates MTORC1 activity to facilitate macroautophagic/autophagic flux. On...
Source: Autophagy - January 5, 2024 Category: Cytology Authors: Peng Huang Rose Yang Dong Pingping Wang Mengnan Xu Xue Sun Xian-Ping Dong Source Type: research
4R MAPT/tau drives endolysosomal and autophagy dysfunction in frontotemporal dementia
Autophagy. 2024 Jan 4. doi: 10.1080/15548627.2023.2300917. Online ahead of print.ABSTRACTDysfunction of the neuronal endolysosome and macroautophagy/autophagy pathway is emerging as an important pathogenic mechanism in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The VCP (valosin-containing protein) gene is of significant relevance, directly implicated in both FTD and ALS. In our recent study, we used patient-derived stem cells to study the effects of VCP mutations on the endolysosome and autophagy system in human cortical excitatory neurons. We found that VCP mutations cause an abnormal accumulat...
Source: Autophagy - January 4, 2024 Category: Cytology Authors: Christy Hung Rickie Patani Source Type: research
Targeting cancer-associated fibroblast autophagy renders pancreatic cancer eradicable with immunochemotherapy by inhibiting adaptive immune resistance
Autophagy. 2024 Jan 4. doi: 10.1080/15548627.2023.2300913. Online ahead of print.ABSTRACTAccumulating evidence suggests that cancer-associated fibroblast (CAF) macroautophagy/autophagy is crucial in tumor development and may be a therapeutic target for pancreatic ductal adenocarcinoma (PDAC). However, the role of CAF autophagy during immune surveillance and cancer immunotherapy is unclear. The present study revealed that the inhibition of CAF autophagy suppresses in vivo tumor development in immune-deficient xenografts. This deletion compromises anti-tumor immunity and anti-tumor efficacy both in vitro and in vivo by upreg...
Source: Autophagy - January 4, 2024 Category: Cytology Authors: Xiaozhen Zhang Mengyi Lao Hanshen Yang Kang Sun Yunfei Dong Lihong He Xinchi Jiang Honghui Wu Yangwei Jiang Muchun Li Honggang Ying Xinyuan Liu Jian Xu Yan Chen Hanjia Zhang Ruhong Zhou Jianqing Gao Xueli Bai Tingbo Liang Source Type: research
4R MAPT/tau drives endolysosomal and autophagy dysfunction in frontotemporal dementia
Autophagy. 2024 Jan 4. doi: 10.1080/15548627.2023.2300917. Online ahead of print.ABSTRACTDysfunction of the neuronal endolysosome and macroautophagy/autophagy pathway is emerging as an important pathogenic mechanism in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The VCP (valosin-containing protein) gene is of significant relevance, directly implicated in both FTD and ALS. In our recent study, we used patient-derived stem cells to study the effects of VCP mutations on the endolysosome and autophagy system in human cortical excitatory neurons. We found that VCP mutations cause an abnormal accumulat...
Source: Autophagy - January 4, 2024 Category: Cytology Authors: Christy Hung Rickie Patani Source Type: research
Targeting cancer-associated fibroblast autophagy renders pancreatic cancer eradicable with immunochemotherapy by inhibiting adaptive immune resistance
Autophagy. 2024 Jan 4. doi: 10.1080/15548627.2023.2300913. Online ahead of print.ABSTRACTAccumulating evidence suggests that cancer-associated fibroblast (CAF) macroautophagy/autophagy is crucial in tumor development and may be a therapeutic target for pancreatic ductal adenocarcinoma (PDAC). However, the role of CAF autophagy during immune surveillance and cancer immunotherapy is unclear. The present study revealed that the inhibition of CAF autophagy suppresses in vivo tumor development in immune-deficient xenografts. This deletion compromises anti-tumor immunity and anti-tumor efficacy both in vitro and in vivo by upreg...
Source: Autophagy - January 4, 2024 Category: Cytology Authors: Xiaozhen Zhang Mengyi Lao Hanshen Yang Kang Sun Yunfei Dong Lihong He Xinchi Jiang Honghui Wu Yangwei Jiang Muchun Li Honggang Ying Xinyuan Liu Jian Xu Yan Chen Hanjia Zhang Ruhong Zhou Jianqing Gao Xueli Bai Tingbo Liang Source Type: research
DIRAS3 induces autophagy and enhances sensitivity to anti-autophagic therapy in KRAS-driven pancreatic and ovarian carcinomas
Autophagy. 2024 Jan 3:1-17. doi: 10.1080/15548627.2023.2299516. Online ahead of print.ABSTRACTPancreatic ductal adenocarcinoma (PDAC) and low-grade ovarian cancer (LGSOC) are characterized by the prevalence of KRAS oncogene mutations. DIRAS3 is the first endogenous non-RAS protein that heterodimerizes with RAS, disrupts RAS clustering, blocks RAS signaling, and inhibits cancer cell growth. Here, we found that DIRAS3-mediated KRAS inhibition induces ROS-mediated apoptosis in PDAC and LGSOC cells with KRAS mutations, but not in cells with wild-type KRAS, by downregulating NFE2L2/Nrf2 transcription, reducing antioxidants, and...
Source: Autophagy - January 3, 2024 Category: Cytology Authors: Gamze Bildik Joshua P Gray Weiqun Mao Hailing Yang Rumeysa Ozyurt Vivian R Orellana Olivier De Wever Mark S Carey Robert C Bast Zhen Lu Source Type: research
REEPing the harvest of reticulophagy and nucleophagy
Autophagy. 2024 Jan 1. doi: 10.1080/15548627.2023.2300915. Online ahead of print.ABSTRACTUnder stress conditions, the endoplasmic reticulum and nucleus undergo turnover through selective macroautophagy/autophagy processes termed reticulophagy and nucleophagy, respectively. Our recent study has identified the protein Hva22/Rop1/Yep1, a member of the REEP1-REEP4 subfamily of the REEP protein family, as an essential factor for both processes in the fission yeast Schizosaccharomyces pombe. In the absence of Hva22/Yep1, reticulophagy and nucleophagy cargos without surrounding autophagic membranes accumulate in the cytoplasm. In...
Source: Autophagy - January 2, 2024 Category: Cytology Authors: Chen-Xi Zou Li-Lin Du Source Type: research
An autophagy-independent role of ULK1/ULK2 in mechanotransduction and breast cancer cell migration
Autophagy. 2024 Jan 1. doi: 10.1080/15548627.2023.2300916. Online ahead of print.ABSTRACTThe progression of breast cancer is often accompanied by changes in extracellular matrix stiffness and cell adhesion ability, which are closely related to cellular mechanotransduction. However, the underlying regulatory mechanisms remain mysterious. Our study reveals that the macroautophagy/autophagy-inducing kinases, ULK1 and ULK2, inhibit the assembly of focal adhesions and F-actin by phosphorylating the adhesion protein PXN, to prevent breast cancer cell migration in an autophagy-independent fashion. Interestingly, ULK1/ULK2-mediate...
Source: Autophagy - January 2, 2024 Category: Cytology Authors: Peigang Liang Bo Wang Source Type: research
REEPing the harvest of reticulophagy and nucleophagy
Autophagy. 2024 Jan 1. doi: 10.1080/15548627.2023.2300915. Online ahead of print.ABSTRACTUnder stress conditions, the endoplasmic reticulum and nucleus undergo turnover through selective macroautophagy/autophagy processes termed reticulophagy and nucleophagy, respectively. Our recent study has identified the protein Hva22/Rop1/Yep1, a member of the REEP1-REEP4 subfamily of the REEP protein family, as an essential factor for both processes in the fission yeast Schizosaccharomyces pombe. In the absence of Hva22/Yep1, reticulophagy and nucleophagy cargos without surrounding autophagic membranes accumulate in the cytoplasm. In...
Source: Autophagy - January 2, 2024 Category: Cytology Authors: Chen-Xi Zou Li-Lin Du Source Type: research
An autophagy-independent role of ULK1/ULK2 in mechanotransduction and breast cancer cell migration
Autophagy. 2024 Jan 1. doi: 10.1080/15548627.2023.2300916. Online ahead of print.ABSTRACTThe progression of breast cancer is often accompanied by changes in extracellular matrix stiffness and cell adhesion ability, which are closely related to cellular mechanotransduction. However, the underlying regulatory mechanisms remain mysterious. Our study reveals that the macroautophagy/autophagy-inducing kinases, ULK1 and ULK2, inhibit the assembly of focal adhesions and F-actin by phosphorylating the adhesion protein PXN, to prevent breast cancer cell migration in an autophagy-independent fashion. Interestingly, ULK1/ULK2-mediate...
Source: Autophagy - January 2, 2024 Category: Cytology Authors: Peigang Liang Bo Wang Source Type: research
Control of nuclear envelope dynamics during acute ER stress by LINC complexes disassembly and selective, asymmetric autophagy of the outer nuclear membrane
Autophagy. 2023 Dec 28. doi: 10.1080/15548627.2023.2299123. Online ahead of print.ABSTRACTThe endoplasmic reticulum (ER) extends to the outer (ONM) and the inner (INM) nuclear membrane forming the nuclear envelope (NE) that delimits the nucleoplasm containing the cell genome. Unfolded protein responses (UPRs) and reticulophagy responses increase or reduce ER size and activities, respectively. If dynamic changes of the ER are transmitted to the contiguous NE was not known. In our recent publication, we report on the transmission of stress-induced ER expansion to the NE, which requires disassembly of the Linker of Nucleoskel...
Source: Autophagy - December 28, 2023 Category: Cytology Authors: Marika K Kuci ńska Maurizio Molinari Source Type: research
Control of nuclear envelope dynamics during acute ER stress by LINC complexes disassembly and selective, asymmetric autophagy of the outer nuclear membrane
Autophagy. 2023 Dec 28. doi: 10.1080/15548627.2023.2299123. Online ahead of print.ABSTRACTThe endoplasmic reticulum (ER) extends to the outer (ONM) and the inner (INM) nuclear membrane forming the nuclear envelope (NE) that delimits the nucleoplasm containing the cell genome. Unfolded protein responses (UPRs) and reticulophagy responses increase or reduce ER size and activities, respectively. If dynamic changes of the ER are transmitted to the contiguous NE was not known. In our recent publication, we report on the transmission of stress-induced ER expansion to the NE, which requires disassembly of the Linker of Nucleoskel...
Source: Autophagy - December 28, 2023 Category: Cytology Authors: Marika K Kuci ńska Maurizio Molinari Source Type: research
