Golgi stress response: A regulatory mechanism of Golgi function

Gao, Jiayin; Gao, Anbo; Liu, Wei; Chen, Linxi

doi:10.1002/biof.1780

Cited by 20 publications

(20 citation statements)

References 94 publications

(91 reference statements)

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“…The Golgi apparatus may also sense and transduce stress signals to maintain homeostasis of the organelle [39,45]. Under Golgi stress conditions, the transcription of Golgi-related genes is upregulated to restore Golgi function [49][50][51]77]. Taniguchi et al [50] reported that the TFE3 transcription factor plays an important role in the expression of Golgi-related genes in response to Golgi stress.…”

Section: Discussionmentioning

confidence: 99%

PKM2 controls the translation of TFE3 to maintain the integrity of the Golgi apparatus for the survival of HeLa and ME‐180 cervical cancer cells

2023

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The M2 isoform of pyruvate kinase (PKM2) is abundantly expressed in various cancer cells and associated with tumorigenesis, tumour proliferation and tumour progression. However, the role of PKM2 in these oncological processes is not fully understood. In the present study, we depleted PKM2 expression using RNA interference (RNAi), which induced apoptotic cell death and was accompanied by the downregulation of GM130, giantin, and p115 in HeLa and ME‐180 cervical cancer cells. The decreased expression of these proteins caused structural and functional disturbances in the Golgi apparatus, which manifested as the dispersion of the Golgi apparatus and delayed anterograde trafficking from the ER to the Golgi. The transcription factor, TFE3, which functions in the Golgi stress response, was responsible for the expression of GM130, giantin, and p115 that maintained the integrity of the organelle under normal growth conditions. In PKM2‐knockdown cells, the translation of TFE3 was markedly reduced. Knockdown of TFE3 by RNAi resulted in the downregulation of GM130, giantin, and p115, dispersion of the Golgi apparatus, and apoptotic cell death, similar to those observed following PKM2 knockdown. Conversely, the exogenous expression of TFE3 in PKM2 knockdown cells partially mitigated the aforementioned effects. We also demonstrated that PKM2 bound to the 5′ UTR on TFE3 mRNA and promoted translation. This study is the first to identify a new function for PKM2, which activates the basal Golgi stress response to maintain the integrity of the Golgi apparatus through the translation of TFE3 and promote cancer cell survival.

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Section: Discussionmentioning

confidence: 99%

PKM2 controls the translation of TFE3 to maintain the integrity of the Golgi apparatus for the survival of HeLa and ME‐180 cervical cancer cells

2023

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“…The Golgi stress response is a relatively recently proposed stress signal that is less well understood than ER stress, which is caused by dysfunction of the nearby organelle, the ER [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Until now, Golgi stress has been classified by several signaling pathways, including TFE3, CREB3, and Hsp47 [ 15 , 16 , 17 ]; however, there remain many unresolved issues, such as the endogenous stimuli that cause Golgi stress and the downstream factors of these stress sensors. We previously characterized the processing and degradation of CREB3 in a mouse neuroblastoma cell line, Neuro2a [ 19 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…On the contrary, the concept of the Golgi stress response remains obscure. Even under such circumstances, TFE3, CREB3, and Hsp47 have been reported as factors involved in Golgi stress [ 15 , 16 , 17 ]. Several TFE3 target genes (e.g., GM130 and SIAT4A), and an Arf4 gene as a target factor for CREB3, have been reported [ 16 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Elucidation of OSW-1-Induced Stress Responses in Neuro2a Cells

Oh‐hashi

Nakamura

Ogawa

et al. 2023

IJMS

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OSW-1, a steroidal saponin isolated from the bulbs of Ornithogalum saundersiae, is a promising compound for an anticancer drug; however, its cytotoxic mechanisms have not been fully elucidated. Therefore, we analyzed the stress responses triggered by OSW-1 in the mouse neuroblastoma cell line Neuro2a by comparing it with brefeldin A (BFA), a Golgi apparatus-disrupting reagent. Among the Golgi stress sensors TFE3/TFEB and CREB3, OSW-1 induced dephosphorylation of TFE3/TFEB but not cleavage of CREB3, and induction of the ER stress-inducible genes GADD153 and GADD34 was slight. On the other hand, the induction of LC3-II, an autophagy marker, was more pronounced than the BFA stimulation. To elucidate OSW-1-induced gene expression, we performed a comprehensive gene analysis using a microarray method and observed changes in numerous genes involved in lipid metabolism, such as cholesterol, and in the regulation of the ER–Golgi apparatus. Abnormalities in ER–Golgi transport were also evident in the examination of secretory activity using NanoLuc-tag genes. Finally, we established Neuro2a cells lacking oxysterol-binding protein (OSBP), which were severely reduced by OSW-1, but found OSBP deficiency had little effect on OSW-1-induced cell death and the LC3-II/LC3-I ratio in Neuro2a cells. Future work to elucidate the relationship between OSW-1-induced atypical Golgi stress responses and autophagy induction may lead to the development of new anticancer agents.

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“…In mammals, this response involves the activation of the TFE3, heat shock protein 47 (HSP 47), CREB3, E26 transformation specific (ETS), proteoglycan, and mucin pathways. The CREB3 and ETS pathways, for example, can promote apoptosis [ 121 ]. Golgi stress inducers caused ferroptosis in HeLa cells, which can be prevented through SLC7A11 or GPX4 overexpression, as well as ACSL4 depletion [ 122 ].…”

Section: Role Of Different Organelles In Apoptosis and Ferroptosismentioning

confidence: 99%

Organelle-Specific Mechanisms in Crosstalk between Apoptosis and Ferroptosis

Zhang

Duan

et al. 2023

Oxidative Medicine and Cellular Longevity

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Apoptosis has been extensively studied, whereas ferroptosis is a newly discovered form of regulated cell death that involves iron-dependent accumulations of lipid hydroperoxides. While these two cell death mechanisms were initially believed to be mutually exclusive, recent studies have revealed cellular contexts requiring a balanced interaction between them. Numerous subcellular sites and signaling molecules within these sites are involved in both processes, either as modules or switches that allow cells to choose on how to proceed. The close relationships between apoptosis and ferroptosis, as well as the possibility of switching from one to the other, are described in this review. To understand the crosstalk between apoptosis and ferroptosis, various organelle-specific mechanisms must be analyzed and compared. The ability to switch apoptosis to ferroptosis by targeting cellular organelles has a great potential in cancer therapy.

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Golgi stress response: A regulatory mechanism of Golgi function

Cited by 20 publications

References 94 publications

PKM2 controls the translation of TFE3 to maintain the integrity of the Golgi apparatus for the survival of HeLa and ME‐180 cervical cancer cells

PKM2 controls the translation of TFE3 to maintain the integrity of the Golgi apparatus for the survival of HeLa and ME‐180 cervical cancer cells

Elucidation of OSW-1-Induced Stress Responses in Neuro2a Cells

Organelle-Specific Mechanisms in Crosstalk between Apoptosis and Ferroptosis

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