The Nem1/Spo7–Pah1/lipin axis is required for autophagy induction after <scp>TORC</scp>1 inactivation

Rahman, Muhammad Arifur; Mostofa, Md. Golam; Ushimaru, Takashi

doi:10.1111/febs.14448

Cited by 54 publications

(53 citation statements)

References 73 publications

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“…This process is initiated by the fusion of membranes of the cell nucleus and vacuole. The tonoplast protein Vac8 and protein Nvj1, being a part of the nuclear envelope, are involved in the fusion [111] ( Table 2). The next stage is the formation of tonoplast invagination that increases and transforms into an intra-vacuolar vesicle consisting of three membranes (tonoplast and two nuclear envelope membranes) and a portion of the nucleoplasm.…”

Section: Formation Of the Autophagic Body During Microautophagymentioning

confidence: 99%

Completing Autophagy: Formation and Degradation of the Autophagic Body and Metabolite Salvage in Plants

Stefaniak

Wojtyla

Pietrowska‐Borek

et al. 2020

IJMS

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Autophagy is an evolutionarily conserved process that occurs in yeast, plants, and animals. Despite many years of research, some aspects of autophagy are still not fully explained. This mostly concerns the final stages of autophagy, which have not received as much interest from the scientific community as the initial stages of this process. The final stages of autophagy that we take into consideration in this review include the formation and degradation of the autophagic bodies as well as the efflux of metabolites from the vacuole to the cytoplasm. The autophagic bodies are formed through the fusion of an autophagosome and vacuole during macroautophagy and by vacuolar membrane invagination or protrusion during microautophagy. Then they are rapidly degraded by vacuolar lytic enzymes, and products of the degradation are reused. In this paper, we summarize the available information on the trafficking of the autophagosome towards the vacuole, the fusion of the autophagosome with the vacuole, the formation and decomposition of autophagic bodies inside the vacuole, and the efflux of metabolites to the cytoplasm. Special attention is given to the formation and degradation of autophagic bodies and metabolite salvage in plant cells.

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Section: Formation Of the Autophagic Body During Microautophagymentioning

confidence: 99%

Completing Autophagy: Formation and Degradation of the Autophagic Body and Metabolite Salvage in Plants

Stefaniak

Wojtyla

Pietrowska‐Borek

et al. 2020

IJMS

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“…Finally, micro-autophagy can also be induced by TORC1 inactivation under nitrogen starvation in a Nem1/Spo7-dependnt way [9]. However, neither AMPK nor the Nem1/Spo7 phosphatase complex, which regulates membrane domains, specifically promote micro-autophagy and both were implicated also in macro-autophagy [9,10]. Thus, it seems that micro-autophagy can be induced by multiple stresses through multiple signaling pathways, and further research is needed to identify its specific upstream regulators.…”

Section: Macro-versus Micro-autophagymentioning

confidence: 99%

ESCRTing proteasomes to the lysosome

Segev

2020

PLoS Genet

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Clearance of excess or damaged cellular components is crucial for homeostasis and under stress and defects in this process result in multiple diseases, including neurodegeneration [1]. This clearance is done in two sites: the proteasome, which degrades proteins, and the lysosome, which can degrade all macromolecules and organelles. Proteasomes are multi-protein machines composed of a 20S core particle (CP) capped with two regulatory particles (RP), which direct ubiquitinated proteins to the core cavity, where proteases reside [2]. The lysosome, a membrane-bound organelle with an acidic environment, contains diverse degradative enzymes that function in this milieu. In addition to endocytosis, in which endosomes fuse with lysosomes, two other ways lead into the lysosome: macro-autophagy and micro-autophagy. In macro-autophagy, the double-membrane autophagosome (AP) engulfs cargo and fuses with the lysosome, whereas in micro-autophagy cargo is engulfed by the lysosomal membrane itself. While there is plenty of information about macro-autophagy, not much is known about micro-autophagy [3]. In both cases, the membrane engulfing the cargo needs to seal and the mechanism of this sealing has been a major question in the autophagy field. Another question in the degradation field has been how proteasomes recycle. During normal growth of yeast cells, the majority of the proteasomes reside in the nucleus and damaged proteasomes are shuttled to the lysosome via a selective macro-autophagy pathway, proteaphagy [2]. During stress, proteasomes relocate to the cytoplasm. Under nitrogen starvation, macro-autophagy is vastly induced and excess of cellular components, including proteasomes, are delivered to the lysosome (vacuole in yeast) for degradation. It was recently shown that in nitrogen-starvation induced macro-autophagy, ESCRT complexes play a role in sealing APs to allow their fusion with the lysosome [4]. Under glucose starvation, normal proteasomes are stored in proteasome storage granules (PSGs), which dissolve when glucose is added back [2]. However, it was not clear what happens to aberrant proteasomes under carbon stress (Fig 1). Li et al., address this question [5]. They identified the AMPK and ESCRT complexes (see Table 1) in a genome-wide screen for gene-deletion mutants defective in proteasome degradation during glucose starvation and determined their effect on proteasome fate. Their three major findings are: First, under carbon stress, damaged proteasomes are delivered to the lysosome via micro-autophagy in an AMPK-and ESCRT-dependent manner. Second, when AMPK is absent, the CP of proteasomes accumulate in the iPOD, a deposit site for protein aggregates [6]. Third, whereas under nitrogen starvation proteasomes are degraded together with other cellular components, under carbon starvation proteasomes are sorted to different destinations and only damaged proteasomes are degraded (Fig 1). This sorting is an example of a more economical solution of cells to carbon stress than the extensive degradation of cellular comp...

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“…The imbalance of lipid homeostasis in cells lacking PAH1 results in a multitude of other phenotypes that include fatty acid-induced toxicity (100), hypersensitivity to oxidative stress (103), loss in cell wall strength (104,105), reduction in chronological life span (103), the inability to fuse vacuoles (106), the inability to degrade cellular components (e.g. autophagy) (107), and the inability to grow on nonfermentable carbon sources (57,68) and at elevated temperatures (57,68,69). Some of these phenotypes are suppressed by the loss of the DGK1 gene that encodes the CTP-dependent DAG kinase (100,101,108).…”

Section: Epiloguementioning

confidence: 99%

Discoveries of the phosphatidate phosphatase genes in yeast published in the Journal of Biological Chemistry

Carman

2019

Journal of Biological Chemistry

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This review on the discoveries of yeast phosphatidate (PA) phosphatase genes is dedicated to Dr. Herbert Tabor, Editor-in-Chief of JBC for 40 years, on the occasion of his 100th birthday. Here, I reflect on the discoveries of the ,, , and genes encoding all the PA phosphatase enzymes in yeast. PA phosphatase catalyzes PA dephosphorylation to generate diacylglycerol; both substrate and product are key intermediates in the synthesis of membrane phospholipids and triacylglycerol. App1 and Pah1 are peripheral membrane proteins catalyzing an Mg-dependent reaction governed by the DD(T/V) phosphatase motif. Dpp1 and Lpp1 are integral membrane proteins that catalyze an Mg-independent reaction governed by the KRP-PSGH-SRHD phosphatase motif. Pah1 is PA-specific and is the only PA phosphatase responsible for lipid synthesis at the nuclear/endoplasmic reticulum membrane. App1, Dpp1, and Lpp1, respectively, are localized to cortical actin patches and the vacuole and Golgi membranes; they utilize several lipid phosphate substrates, including PA, lysoPA, and diacylglycerol pyrophosphate. App1 is postulated to be involved in endocytosis, whereas Dpp1 and Lpp1 may be involved in lipid signaling. Pah1 is the yeast lipin homolog of mice and humans. A host of cellular defects and lipid-based diseases associated with loss or overexpression of PA phosphatase in yeast, mice, and humans, highlights its importance to cell physiology.

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The Nem1/Spo7–Pah1/lipin axis is required for autophagy induction after TORC1 inactivation

Cited by 54 publications

References 73 publications

Completing Autophagy: Formation and Degradation of the Autophagic Body and Metabolite Salvage in Plants

Completing Autophagy: Formation and Degradation of the Autophagic Body and Metabolite Salvage in Plants

ESCRTing proteasomes to the lysosome

Discoveries of the phosphatidate phosphatase genes in yeast published in the Journal of Biological Chemistry

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