bims-lycede Biomed News
on Lysosome-dependent cell death
Issue of 2025–07–06
two papers selected by
Sofía Peralta, Universidad Nacional de Cuyo
  1. TM9SF3 is a Golgi-resident ATG8-binding protein essential for Golgi-selective autophagy.
  2. Small-molecule probes for imaging and impairing the Golgi apparatus in cancer.
  1. Dev Cell. 2025 Jun 27. pii: S1534-5807(25)00372-7. [Epub ahead of print]
    TM9SF3 is a Golgi-resident ATG8-binding protein essential for Golgi-selective autophagy.
    Jiejie Yang, Yang Dong, Jiaxin Xu, Xuehong Qian, Yang Cai, Yanjun Chen, Pei Zhang, Ding Gao, Zongqiang Cui, Yixian Cui.
      Golgi degradation by selective autophagy (Golgiphagy) requires receptors to direct Golgi fragments into phagophores for sequestration within autophagosomes, followed by lysosomal degradation. Here, we show that the human Golgi transmembrane protein TM9SF3 is a receptor essential for Golgiphagy under nutrient-stress and multiple Golgi-stress conditions. TM9SF3 binds all six mammalian ATG8 proteins through its N-terminal LC3-interacting regions. In U2OS cells, TM9SF3 knockout blocks nutrient-stress-induced Golgi fragmentation and reduces the targeting of Golgi fragments to autophagosomes, resulting in decreased Golgi protein degradation. Beyond nutrient stress, TM9SF3 is required for Golgiphagy induced by monensin, brefeldin A, and disruptions in intra-Golgi protein glycosylation. Knockout of TM9SF3 and mutations in its LC3-interacting regions (LIRs) both compromise protein glycosylation, whereas TM9SF3 overexpression promotes degradation of incompletely glycosylated proteins. Further, we show that TM9SF3 is required for human breast cancer cell proliferation, and high TM9SF3 levels are associated with poor prognosis, implicating its function in breast cancer pathology.
    Keywords:  ATG8; Golgi fragmentation; Golgi stress; Golgiphagy; LC3-interacting region; LIR; TM9SF3; breast cancer; lysosomal degradation; protein glycosylation; receptor
    DOI:  https://doi.org/10.1016/j.devcel.2025.06.017
  2. RSC Med Chem. 2025 Jun 16.
    Small-molecule probes for imaging and impairing the Golgi apparatus in cancer.
    Phanindra Kumar, Poulomi Sengupta, Sudipta Basu.
      The Golgi apparatus (GA) is one of the most important subcellular organelles controlling protein processing, post-translational modification and secretion. Dysregulation of the GA structure and function leads to multiple pathological states, including cancer development and metastasis. Consequently, visualizing GA dynamic structures and their impairment in cancer has emerged as a novel strategy for next-generation unorthodox cancer therapeutics. However, the major challenge in GA-mediated theranostic probe development is the specific targeting of the GA within the subcellular milieu due to the lack of GA-recognizing chemical entities. In this review, we delineated various chemical functionalities that are extensively used as GA-homing moieties. Moreover, we outlined GA imaging probes consisting of classical fluorophores as well as novel aggregation-induced emissive (AIE) probes tagged with GA-homing moieties. Furthermore, we described GA-impairing molecules that can damage GA morphology through chemotherapeutic and photodynamic therapy (PDT) in cancer. Finally, we addressed the current challenges in this emerging and underexplored field of GA-targeted theranostics and proposed potential solutions to guide future cancer therapeutics.
    DOI:  https://doi.org/10.1039/d5md00320b
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