The biological function of cytoplasm-translocated ENDOG (endonuclease G)
Autophagy. 2023 Oct 27:1-3. doi: 10.1080/15548627.2023.2271750. Online ahead of print.ABSTRACTENDOG, a mitochondrial intermembrane space located endonuclease, participates in DNA fragmentation and apoptosis by translocating to the nucleus. ENDOG can also relocate to the mitochondrial matrix, where it regulates mitochondrial genome cleavage. However, the biological function of cytoplasm-translocated ENDOG remains unclear. Our previous study reported that starvation induces the release of ENDOG from mitochondria to the cytoplasm, promoting macroautophagy/autophagy in a process conserved across species. We demonstrate that EN...
Source: Autophagy - October 27, 2023 Category: Cytology Authors: Wenjun Wang Jianshuang Li Qinghua Zhou Source Type: research
The biological function of cytoplasm-translocated ENDOG (endonuclease G)
Autophagy. 2023 Oct 27:1-3. doi: 10.1080/15548627.2023.2271750. Online ahead of print.ABSTRACTENDOG, a mitochondrial intermembrane space located endonuclease, participates in DNA fragmentation and apoptosis by translocating to the nucleus. ENDOG can also relocate to the mitochondrial matrix, where it regulates mitochondrial genome cleavage. However, the biological function of cytoplasm-translocated ENDOG remains unclear. Our previous study reported that starvation induces the release of ENDOG from mitochondria to the cytoplasm, promoting macroautophagy/autophagy in a process conserved across species. We demonstrate that EN...
Source: Autophagy - October 27, 2023 Category: Cytology Authors: Wenjun Wang Jianshuang Li Qinghua Zhou Source Type: research
ATG9 resides on a unique population of small vesicles in presynaptic nerve terminals
Autophagy. 2023 Oct 26. doi: 10.1080/15548627.2023.2274204. Online ahead of print.ABSTRACTIn neurons, autophagosome biogenesis occurs mainly in distal axons, followed by maturation during retrograde transport. Autophagosomal growth depends on the supply of membrane lipids which requires small vesicles containing ATG9, a lipid scramblase essential for macroautophagy/autophagy. Here, we show that ATG9-containing vesicles are enriched in synapses and resemble synaptic vesicles in size and density. The proteome of ATG9-containing vesicles immuno-isolated from nerve terminals showed conspicuously low levels of trafficking prote...
Source: Autophagy - October 26, 2023 Category: Cytology Authors: Beyenech Binotti Momchil Ninov Andreia P Cepeda Marcelo Ganzella Ulf Matti Dietmar Riedel Henning Urlaub Sivakumar Sambandan Reinhard Jahn Source Type: research
ATG9 resides on a unique population of small vesicles in presynaptic nerve terminals
Autophagy. 2023 Oct 26. doi: 10.1080/15548627.2023.2274204. Online ahead of print.ABSTRACTIn neurons, autophagosome biogenesis occurs mainly in distal axons, followed by maturation during retrograde transport. Autophagosomal growth depends on the supply of membrane lipids which requires small vesicles containing ATG9, a lipid scramblase essential for macroautophagy/autophagy. Here, we show that ATG9-containing vesicles are enriched in synapses and resemble synaptic vesicles in size and density. The proteome of ATG9-containing vesicles immuno-isolated from nerve terminals showed conspicuously low levels of trafficking prote...
Source: Autophagy - October 26, 2023 Category: Cytology Authors: Beyenech Binotti Momchil Ninov Andreia P Cepeda Marcelo Ganzella Ulf Matti Dietmar Riedel Henning Urlaub Sivakumar Sambandan Reinhard Jahn Source Type: research
A liaison between chaperone-mediated autophagy and exocytotic lysosomes controls the dendritic metastable proteome
Autophagy. 2023 Oct 24. doi: 10.1080/15548627.2023.2274256. Online ahead of print.ABSTRACTThe neuronal metastable proteome includes several aggregation-prone proteins related to neurodegeneration. The complex morphology of neurons with very thin processes and enhanced protein turnover therefore necessitates efficient local machinery to remove excessive protein. In recent work we revealed that chaperone-mediated autophagy (CMA) provides cargo for dendritic exocytic lysosomes, a mechanism that serves in the rapid removal of disease-relevant, supersaturated proteins such as TARDBP/TDP-43 (TAR DNA binding protein) and HTT (hun...
Source: Autophagy - October 25, 2023 Category: Cytology Authors: Katarzyna M Grochowska Michael R Kreutz Source Type: research
Phase transition and lysosomal degradation of expanded CAG repeat RNA suppress global protein synthesis
Autophagy. 2023 Oct 24. doi: 10.1080/15548627.2023.2274208. Online ahead of print.ABSTRACTPhase transitions (PT) of biomolecules are heavily involved in neurodegenerative disorders. Almost all previous studies were focusing on the PT of misfolded proteins whereas RNA molecules containing expanded repeats such as the CAG repeats are also able to undergo PT in vitro, a process called RNA gelation. Meanwhile, the expanded CAG repeat (eCAGr) RNA forms condensates that are largely observed only in the nuclei and exhibit liquid-like properties without obvious gelation. Thus, whether eCAGr RNA gelation occurs in cells and what fu...
Source: Autophagy - October 25, 2023 Category: Cytology Authors: Junmei Lu Yuyin Pan Xinran Feng Boxun Lu Source Type: research
The NLRX1-SLC39A7 complex orchestrates mitochondrial dynamics and mitophagy to rejuvenate intervertebral disc by modulating mitochondrial Zn < sup > 2+ < /sup > trafficking
Autophagy. 2023 Oct 24. doi: 10.1080/15548627.2023.2274205. Online ahead of print.ABSTRACTIntervertebral disc degeneration (IDD) is the most critical pathological factor in the development of low back pain. The maintenance of nucleus pulposus (NP) cell and intervertebral disc integrity benefits largely from well-controlled mitochondrial quality, surveilled by mitochondrial dynamics (fission and fusion) and mitophagy, but the outcome is cellular context-dependent that remain to be clarified. Our studies revealed that the loss of NLRX1 is correlated with NP cell senescence and IDD progression, which involve disordered mitoch...
Source: Autophagy - October 25, 2023 Category: Cytology Authors: Yu Song Huaizhen Liang Gaocai Li Liang Ma Dingchao Zhu Weifeng Zhang Bide Tong Shuai Li Yong Gao Xinghuo Wu Yukun Zhang Xiaobo Feng Kun Wang Cao Yang Source Type: research
Excessive BNIP3- and BNIP3L-dependent mitophagy underlies the pathogenesis of FBXL4-mutated mitochondrial DNA depletion syndrome
Autophagy. 2023 Oct 24. doi: 10.1080/15548627.2023.2274260. Online ahead of print.ABSTRACTMitophagy, the process of removing damaged mitochondria to promote cell survival, plays a crucial role in cellular functionality. However, excessive, or uncontrolled mitophagy can lead to reduced mitochondrial content that burdens the remaining organelles, triggering mitophagy-mediated cell death. FBXL4 mutations, which affect the substrate-binding adaptor of the CUL1 (cullin 1)-RING ubiquitin ligase complex (CRL1), have been linked to mitochondrial DNA depletion syndrome type 13 (MTDPS13) characterized by reduced mtDNA content and im...
Source: Autophagy - October 25, 2023 Category: Cytology Authors: Kun Gao Yingji Chen Ren Mo Chenji Wang Source Type: research
The role of ATG5 beyond Atg8ylation and autophagy
This study shows that in the absence of ATG5, but not other core canonical autophagy factors, endolysosomal organelles display a lysosomal hypersensitivity phenotype when subjected to damage. This is in part due to a compromised recruitment of ESCRT proteins to lysosomes in need of repair. Mechanistically, in the absence of ATG5, the ESCRT protein PDCD6IP/ALIX is sequestered by the alternative conjugate ATG12-ATG3, contributing to excessive exocytic processes while not being available for lysosomal repair. Specifically, this condition increases secretion of extracellular vesicles and particles, and leads to excessive degra...
Source: Autophagy - October 25, 2023 Category: Cytology Authors: Fulong Wang Einar S Trosdal Masroor Ahmad Paddar Thabata L A Duque Lee Allers Michal Mudd Prithvi R Akepati Ruheena Javed Jingyue Jia Michelle Salemi Brett Phinney Vojo Deretic Source Type: research
RUNDC1 negatively mediates the fusion of autophagosomes with lysosomes via regulating SNARE complex assembly
Autophagy. 2023 Oct 24. doi: 10.1080/15548627.2023.2274210. Online ahead of print.ABSTRACTMacroautophagy/autophagy is an essential pro-survival mechanism activated in response to nutrient deficiency. The proper fusion between autophagosomes and lysosomes is a critical step for autophagic degradation. We recently reported that RUNDC1 (RUN domain containing 1) inhibits autolysosome formation via clasping the ATG14-STX17-SNAP29 complex to hinder VAMP8 binding. We showed that RUNDC1 colocalizes with LC3 and associates with mature autophagosomes in cell lines and the zebrafish model. We utilized liposome fusion and in vitro aut...
Source: Autophagy - October 25, 2023 Category: Cytology Authors: Rui Zhang Vincenzo Torraca Hao Lyu Shuai Xiao Dong Guo Cefan Zhou Jingfeng Tang Source Type: research
A liaison between chaperone-mediated autophagy and exocytotic lysosomes controls the dendritic metastable proteome
Autophagy. 2023 Oct 24. doi: 10.1080/15548627.2023.2274256. Online ahead of print.ABSTRACTThe neuronal metastable proteome includes several aggregation-prone proteins related to neurodegeneration. The complex morphology of neurons with very thin processes and enhanced protein turnover therefore necessitates efficient local machinery to remove excessive protein. In recent work we revealed that chaperone-mediated autophagy (CMA) provides cargo for dendritic exocytic lysosomes, a mechanism that serves in the rapid removal of disease-relevant, supersaturated proteins such as TARDBP/TDP-43 (TAR DNA binding protein) and HTT (hun...
Source: Autophagy - October 25, 2023 Category: Cytology Authors: Katarzyna M Grochowska Michael R Kreutz Source Type: research
Phase transition and lysosomal degradation of expanded CAG repeat RNA suppress global protein synthesis
Autophagy. 2023 Oct 24. doi: 10.1080/15548627.2023.2274208. Online ahead of print.ABSTRACTPhase transitions (PT) of biomolecules are heavily involved in neurodegenerative disorders. Almost all previous studies were focusing on the PT of misfolded proteins whereas RNA molecules containing expanded repeats such as the CAG repeats are also able to undergo PT in vitro, a process called RNA gelation. Meanwhile, the expanded CAG repeat (eCAGr) RNA forms condensates that are largely observed only in the nuclei and exhibit liquid-like properties without obvious gelation. Thus, whether eCAGr RNA gelation occurs in cells and what fu...
Source: Autophagy - October 25, 2023 Category: Cytology Authors: Junmei Lu Yuyin Pan Xinran Feng Boxun Lu Source Type: research
The NLRX1-SLC39A7 complex orchestrates mitochondrial dynamics and mitophagy to rejuvenate intervertebral disc by modulating mitochondrial Zn < sup > 2+ < /sup > trafficking
Autophagy. 2023 Oct 24. doi: 10.1080/15548627.2023.2274205. Online ahead of print.ABSTRACTIntervertebral disc degeneration (IDD) is the most critical pathological factor in the development of low back pain. The maintenance of nucleus pulposus (NP) cell and intervertebral disc integrity benefits largely from well-controlled mitochondrial quality, surveilled by mitochondrial dynamics (fission and fusion) and mitophagy, but the outcome is cellular context-dependent that remain to be clarified. Our studies revealed that the loss of NLRX1 is correlated with NP cell senescence and IDD progression, which involve disordered mitoch...
Source: Autophagy - October 25, 2023 Category: Cytology Authors: Yu Song Huaizhen Liang Gaocai Li Liang Ma Dingchao Zhu Weifeng Zhang Bide Tong Shuai Li Yong Gao Xinghuo Wu Yukun Zhang Xiaobo Feng Kun Wang Cao Yang Source Type: research
Excessive BNIP3- and BNIP3L-dependent mitophagy underlies the pathogenesis of FBXL4-mutated mitochondrial DNA depletion syndrome
Autophagy. 2023 Oct 24. doi: 10.1080/15548627.2023.2274260. Online ahead of print.ABSTRACTMitophagy, the process of removing damaged mitochondria to promote cell survival, plays a crucial role in cellular functionality. However, excessive, or uncontrolled mitophagy can lead to reduced mitochondrial content that burdens the remaining organelles, triggering mitophagy-mediated cell death. FBXL4 mutations, which affect the substrate-binding adaptor of the CUL1 (cullin 1)-RING ubiquitin ligase complex (CRL1), have been linked to mitochondrial DNA depletion syndrome type 13 (MTDPS13) characterized by reduced mtDNA content and im...
Source: Autophagy - October 25, 2023 Category: Cytology Authors: Kun Gao Yingji Chen Ren Mo Chenji Wang Source Type: research
The role of ATG5 beyond Atg8ylation and autophagy
This study shows that in the absence of ATG5, but not other core canonical autophagy factors, endolysosomal organelles display a lysosomal hypersensitivity phenotype when subjected to damage. This is in part due to a compromised recruitment of ESCRT proteins to lysosomes in need of repair. Mechanistically, in the absence of ATG5, the ESCRT protein PDCD6IP/ALIX is sequestered by the alternative conjugate ATG12-ATG3, contributing to excessive exocytic processes while not being available for lysosomal repair. Specifically, this condition increases secretion of extracellular vesicles and particles, and leads to excessive degra...
Source: Autophagy - October 25, 2023 Category: Cytology Authors: Fulong Wang Einar S Trosdal Masroor Ahmad Paddar Thabata L A Duque Lee Allers Michal Mudd Prithvi R Akepati Ruheena Javed Jingyue Jia Michelle Salemi Brett Phinney Vojo Deretic Source Type: research
