MAMs are attractive targets for bacterial repurposing of the host cell

Escoll, Pedro; Rolando, Monica; Buchrieser, Carmen

doi:10.1002/bies.201600171

Cited by 16 publications

(6 citation statements)

References 58 publications

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“…It is tempting to speculate that these sites of TbSpl enrichment may represent contact sites between the ER and the mitochondrial outer membrane, a sub-compartment of ER and mitochondria commonly known as mitochondria associated membranes (MAMs) 41 . Interestingly, it has been speculated before that SPL may be located in MAMs 3,42 .…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial sphingosine-1-phosphate lyase is essential for phosphatidylethanolamine synthesis and survival of Trypanosoma brucei

Nejad

Stumpe

Rauch

et al. 2020

Sci Rep

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Sphingosine-1-phosphate is a signaling molecule involved in the control of cell migration, differentiation, survival and other physiological processes. This sphingolipid metabolite can be degraded by the action of sphingosine-1-phosphate lyase (SPL) to form hexadecenal and ethanolamine phosphate. The importance of SPL-mediated ethanolamine phosphate formation has been characterized in only few cell types. We show that in the protozoan parasite Trypanosoma brucei, expression of TbSpl is essential for cell survival. Ablation of TbSpl expression increased sphingosine-1-phosphate levels and reduced de novo formation and steady-state levels of the glycerophospholipid phosphatidylethanolamine (PE). Growth of TbSpl-depleted parasites could be in part rescued by ethanolamine supplementation to the growth medium, indicating that the main function of TbSpl is to provide ethanolamine phosphate for PE synthesis. In contrast to most cell types analyzed, where SPL localizes to the endoplasmic reticulum, we found by high-resolution microscopy that TbSpl is a mitochondrial protein. In spite of its mitochondrial localization, TbSpl depletion had no apparent effect on mitochondrial morphology but resulted in aggregation of acidocalcisomes. Our results link mitochondria to sphingolipid metabolism and suggest possible roles for PE in acidocalcisome function. Sphingosine-1-phosphate (S1P) is a sphingolipid metabolite involved in the control of cell migration, differentiation and survival, as well as numerous other (patho-)physiological processes (reviewed in 1-5). S1P levels are regulated through the actions of three enzyme activities: i) sphingosine kinase synthesizes S1P by phosphorylating the long chain base sphingosine, ii) sphingosine phosphohydrolases catalyze the reverse reaction to produce sphingosine, and iii) sphingosine-1-phosphate lyase (SPL) irreversibly degrades S1P by cleaving the acyl chain between carbon atoms 2 and 3, resulting in the formation of hexadecenal and ethanolamine phosphate (reviewed in 3,6). Ethanolamine phosphate, in turn, may represent a substrate for phosphatidylethanolamine (PE) synthesis by the CDP-ethanolamine branch of the Kennedy pathway 7. SPL is dependent on pyridoxal 5′-phosphate as cofactor for enzymatic activity 8. In mammals and yeast, SPL is membrane-bound via a single N-terminal transmembrane domain, which is not strictly required for in vitro enzyme activity 9,10. In contrast, at least in Saccharomyces cerevisiae, the transmembrane domain is necessary for SPL activity in vivo and may be involved in oligomer formation 10. The structure has been solved for bacterial SPL homologues 11-13 and soluble forms of human 9,14 and yeast 11 SPL. Cytosolically produced S1P can be secreted into the extracellular environment via specific transporters (reviewed in 6), where it binds to cell surface G protein-coupled receptors, known in mammals as S1PR 1-5 (reviewed by 15-17), to induce numerous cellular and tissue-specific responses. Alternatively, S1P can act as

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Section: Discussionmentioning

confidence: 99%

Mitochondrial sphingosine-1-phosphate lyase is essential for phosphatidylethanolamine synthesis and survival of Trypanosoma brucei

Nejad

Stumpe

Rauch

et al. 2020

Sci Rep

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“…Finally, L. pneumophila effectors not only localize to LCV-ER MCS but also target mitochondria-ER contact sites (Murata et al 2022 ). Mitochondria-ER-associated membranes (MAMs) are implicated in various cellular functions, including lipid synthesis and trafficking, mitochondrial morphology, inflammasome activation, autophagosome formation, and apoptosis (Escoll et al 2017 ). The L. pneumophila effector Lpg1137 binds the MAM- and mitochondria-enriched phospholipid phosphatidic acid and proteolytically degrades the MAM-localizing SNARE syntaxin 17 (Murata et al 2022 ).…”

Section: Subversion Of Membrane Contact Sites By Bacterial Pathogensmentioning

confidence: 99%

Pathogen vacuole membrane contact sites – close encounters of the fifth kind

et al. 2023

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Vesicular trafficking and membrane fusion are well-characterized, versatile, and sophisticated means of ‘long range’ intracellular protein and lipid delivery. Membrane contact sites (MCS) have been studied in far less detail, but are crucial for ‘short range’ (10-30 nm) communication between organelles, as well as between pathogen vacuoles and organelles. MCS are specialized in the non-vesicular trafficking of small molecules such as calcium and lipids. Pivotal MCS components important for lipid transfer are the VAP receptor/tether protein, oxysterol binding proteins (OSBPs), the ceramide transport protein CERT, the phosphoinositide phosphatase Sac1, and the lipid phosphatidylinositol 4-phosphate (PtdIns(4)P). In this review, we discuss how these MCS components are subverted by bacterial pathogens and their secreted effector proteins to promote intracellular survival and replication.

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“…STX17 interacts with ATG14 before recruiting the PI3K complex to the MAMs in autophagosome biogenesis [66]. Legionella effector sphingosine-1 phosphate lyase activity (LpSpl) is a T4SS secreted effector from L. pneumophila that appears to target MAMs to modulate the autophagy response to infection [99,100].…”

Section: Mams Positively Regulate Autophagymentioning

confidence: 99%

Mitochondria-Associated Endoplasmic Reticulum Membranes: Inextricably Linked with Autophagy Process

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Mitochondria-associated membranes (MAMs), physical connection sites between the endoplasmic reticulum (ER) and the outer mitochondrial membrane (OMM), are involved in numerous cellular processes, such as calcium ion transport, lipid metabolism, autophagy, ER stress, mitochondria morphology, and apoptosis. Autophagy is a highly conserved intracellular process in which cellular contents are delivered by double-membrane vesicles, called autophagosomes, to the lysosomes for destruction and recycling. Autophagy, typically triggered by stress, eliminates damaged or redundant protein molecules and organelles to maintain regular cellular activity. Dysfunction of MAMs or autophagy is intimately associated with various diseases, including aging, cardiovascular, infections, cancer, multiple toxic agents, and some genetic disorders. Increasing evidence has shown that MAMs play a significant role in autophagy development and maturation. In our study, we concentrated on two opposing functions of MAMs in autophagy: facilitating the formation of autophagosomes and inhibiting autophagy. We recognized the link between MAMs and autophagy in the occurrence and progression of the diseases and therefore collated and summarized the existing intrinsic molecular mechanisms. Furthermore, we draw attention to several crucial data and open issues in the area that may be helpful for further study.

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MAMs are attractive targets for bacterial repurposing of the host cell

Cited by 16 publications

References 58 publications

Mitochondrial sphingosine-1-phosphate lyase is essential for phosphatidylethanolamine synthesis and survival of Trypanosoma brucei

Mitochondrial sphingosine-1-phosphate lyase is essential for phosphatidylethanolamine synthesis and survival of Trypanosoma brucei

Pathogen vacuole membrane contact sites – close encounters of the fifth kind

Mitochondria-Associated Endoplasmic Reticulum Membranes: Inextricably Linked with Autophagy Process

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