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

ATG12-ATG5-TECPR1: an alternative E3-like complex utilized during the cellular response to lysosomal membrane damage
Autophagy. 2023 Oct 23:1-2. doi: 10.1080/15548627.2023.2267414. Online ahead of print.ABSTRACTATG16L1 is an essential component of the Atg8-family protein conjugation machinery, providing membrane targeting for the ATG12-ATG5 conjugate. Recently, we identified an alternative E3-like complex that functions independently of ATG16L1. This complex utilizes the autophagosome-lysosome tethering factor TECPR1 for membrane targeting. TECPR1 is recruited to damaged lysosomal membranes via a direct interaction with sphingomyelin. At the damaged membrane, TECPR1 assembles into an E3-like complex with ATG12-ATG5 to regulate unconventi...
Source: Autophagy - October 24, 2023 Category: Cytology Authors: Dale P Corkery Yao-Wen Wu Source Type: research

This is a public service announcement-BioRender has issued a recall of their autophagy template
Autophagy. 2023 Oct 18:3031-3032. doi: 10.1080/15548627.2023.2266977. Online ahead of print.ABSTRACTI have been surprised at the number of papers I edit where the schematic of macroautophagy/autophagy is wrong, and it is wrong in the same way. How could this happen? Did people get together and agree to misrepresent the morphological intermediates of autophagy? Not exactly.PMID:37850823 | DOI:10.1080/15548627.2023.2266977 (Source: Autophagy)
Source: Autophagy - October 18, 2023 Category: Cytology Authors: Daniel J Klionsky Source Type: research