PIds (phosphoinositides) are phosphorylated derivatives of the membrane phospholipid PtdIns that have emerged as key regulators of many aspects of cellular physiology. We have discovered a PtdIns3P-synthesizing activity in peroxisomes of Saccharomyces cerevisiae and have demonstrated that the lipid kinase Vps34p is already associated with peroxisomes during biogenesis. However, although Vps34 is required, it is not essential for optimal peroxisome biogenesis. The function of Vps34p-containing complex I as well as a subset of PtdIns3P-binding proteins proved to be mandatory for the regulated degradation of peroxisomes. This demonstrates that PtdIns3P-mediated signalling is required for pexophagy.
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http://dx.doi.org/10.1042/BJ20101115 | DOI Listing |
Autophagy
January 2025
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
The synthesis of membrane and secreted proteins is safeguarded by an endoplasmic reticulum-associated ribosome quality control (ER-RQC) that promotes the disposal of defective translation products by the proteasome or via a lysosome-dependent pathway involving the degradation of portions of the ER by macroautophagy (reticulophagy). The UFMylation of RPL26 on ER-stalled ribosomes is essential for activating the ER-RQC and reticulophagy. Here, we report that the viral deubiquitinase (vDUB) encoded in the N-terminal domain of the Epstein-Barr virus (EBV) large tegument protein BPLF1 hinders the UFMylation of RPL26 on ribosomes that stall at the ER, promotes the stabilization of ER-RQC substrates, and inhibits reticulophagy.
View Article and Find Full Text PDFAutophagy
January 2025
Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Although the relationship between macroautophagy/autophagy and Alzheimer disease (AD) is widely studied, the underlying mechanisms are poorly understood, especially the regulatory role of the initiation signaling of autophagy on AD. Here, we find that the ER transmembrane protein CANX (calnexin) is a novel interaction partner of the autophagy-inducing kinase ULK1 and is required for ULK1 recruitment to the ER under basal or starved conditions. Loss of CANX results in the inactivity of ULK1 kinase and inhibits autophagy flux.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia.
The TRAPP (TRAnsport Protein Particle) protein complex is a multi-subunit complex involved in vesicular transport between intracellular compartments. The TRAPP complex plays an important role in endoplasmic reticulum-to-Golgi and Golgi-to-plasma membrane transport, as well as autophagy. TRAPP complexes comprise a core complex, TRAPPI, and the association of peripheral protein subunits to make two complexes, known as TRAPPII and TRAPPIII, which act as Guanine Nucleotide Exchange Factors (GEFs) of Rab11 and Rab1, respectively.
View Article and Find Full Text PDFAutophagy
January 2025
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing, China.
Autophagy
December 2024
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Intervertebral disc degeneration (IVDD) is a leading cause of low back pain that incurs large socioeconomic burdens. Growing evidence reveals that macroautophagy/autophagy dysregulation contributes to IVDD, but the exact role of autophagy and its regulatory mechanisms remain largely unknown. Here, we found that mechanical overloading impaired the autophagic flux of nucleus pulposus (NP) cells and .
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