Regulation of sphingolipid synthesis by the G1/S transcription factor Swi4

Matos, Gabriel S.; Madeira, Juliana B.; Fernandes, Caroline Mota; Dasilva, Deveney; Masuda, Cláudio A.; Poeta, Maurizio Del; Montero-Lomelı́, Mónica

doi:10.1016/j.bbalip.2021.158983

Cited by 4 publications

(2 citation statements)

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“…We still have a limited understanding of how cells sense the levels of sphingolipids and MCS-mediated processes are regulated and coordinated to maintain sphingolipid homeostasis. Furthermore, the molecular mechanisms of sphingolipid homeostasis at the transcriptional level and their upstream signaling cascades are poorly understood, although some enzymes involved in sphingolipid metabolism have been shown to be transcriptionally regulated [70,148,149] (Figure 1B).…”

Section: Discussionmentioning

confidence: 99%

Membrane Contact Sites in Yeast: Control Hubs of Sphingolipid Homeostasis

2021

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Sphingolipids are the most diverse class of membrane lipids, in terms of their structure and function. Structurally simple sphingolipid precursors, such as ceramides, act as intracellular signaling molecules in various processes, including apoptosis, whereas mature and complex forms of sphingolipids are important structural components of the plasma membrane. Supplying complex sphingolipids to the plasma membrane, according to need, while keeping pro-apoptotic ceramides in check is an intricate task for the cell and requires mechanisms that tightly control sphingolipid synthesis, breakdown, and storage. As each of these processes takes place in different organelles, recent studies, using the budding yeast Saccharomyces cerevisiae, have investigated the role of membrane contact sites as hubs that integrate inter-organellar sphingolipid transport and regulation. In this review, we provide a detailed overview of the findings of these studies and put them into the context of established regulatory mechanisms of sphingolipid homeostasis. We have focused on the role of membrane contact sites in sphingolipid metabolism and ceramide transport, as well as the mechanisms that prevent toxic ceramide accumulation.

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Section: Discussionmentioning

confidence: 99%

Membrane Contact Sites in Yeast: Control Hubs of Sphingolipid Homeostasis

2021

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“…Additional candidate substrates for Ypk1 (and Ypk2) have been discussed previously [ 2 , 145 ], but are less well characterized, in that they have not been shown to be directly phosphorylated by Ypk1 either in vitro or in vivo , and/or the sites of phosphorylation have not been mapped, and/or the phenotypic consequences of preventing phosphorylation at demonstrated Ypk1 sites have not been examined. Since that time, Ypk1 action has been implicated in other processes [ 155 ], but by what specific mechanism is less clear, including preventing chromosome fragmentation in response to insults that cause double-stranded DNA breaks [ 229 ], suggesting that lipids other than PtdIns4,5P2 may regulate TORC2 signaling [ 197 ], influencing the expression of the gene encoding Atg8 (mammalian orthologs are GABARAPs) by the transcription factors Msn2 and Msn4 [ 230 ], and affecting the function of the transcription factor Swi4 [ 231 ]. It has also been noted that Ypk1 is able to phosphorylate a site (S232) very near the C-terminus of the ribosomal 40S subunit protein Rps6, but its physiological impact is unclear [ 232 ].…”

Section: Functions Of Ypk1mentioning

confidence: 99%

TOR complex 2 is a master regulator of plasma membrane homeostasis

Thorner

2022

Biochemical Journal

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As first demonstrated in budding yeast (Saccharomyces cerevisiae), all eukaryotic cells contain two, distinct multi-component protein kinase complexes that each harbor the TOR (Target Of Rapamycin) polypeptide as the catalytic subunit. These ensembles, dubbed TORC1 and TORC2, function as universal, centrally important sensors, integrators, and controllers of eukaryotic cell growth and homeostasis. TORC1, activated on the cytosolic surface of the lysosome (or, in yeast, on the cytosolic surface of the vacuole), has emerged as a primary nutrient sensor that promotes cellular biosynthesis and suppresses autophagy. TORC2, located primarily at the plasma membrane, plays a major role in maintaining the proper levels and bilayer distribution of all plasma membrane components (sphingolipids, glycerophospholipids, sterols, and integral membrane proteins). This article surveys what we have learned about signaling via the TORC2 complex, largely through studies conducted in S. cerevisiae. In this yeast, conditions that challenge plasma membrane integrity can, depending on the nature of the stress, stimulate or inhibit TORC2, resulting in, respectively, up-regulation or down-regulation of the phosphorylation and thus the activity of its essential downstream effector the AGC family protein kinase Ypk1. Through the ensuing effect on the efficiency with which Ypk1 phosphorylates multiple substrates that control diverse processes, membrane homeostasis is maintained. Thus, the major focus here is on TORC2, Ypk1, and the multifarious targets of Ypk1 and how the functions of these substrates are regulated by their Ypk1-mediated phosphorylation, with emphasis on recent advances in our understanding of these processes.

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