Yeast Lipin 1 Orthologue Pah1p Regulates Vacuole Homeostasis and Membrane Fusion

Sasser, Terry; Qiu, Quan‐Sheng; Karunakaran, Surya; Padolina, Mark; Reyes, Anna; Flood, Blake A.; Smith, Sheena N.; Gonzales, Chad; Fratti, Rutilio A.

doi:10.1074/jbc.m111.317420

Cited by 93 publications

(153 citation statements)

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“…Cells defective in Pah1 activity also displayed vacuolar fragmentation and decreased vacuolar fusion consistent with the observed reduction in vacuolar recruitment of several protein factors implicated in the vacuolar fusion process (40). Of interest, Pah1 has also been associated with the vacuolar membrane and the conversion from PA to DAG was proposed as a critical event leading to vacuole fusion (40).…”

Section: Pa Directly Binds Transcriptional Regulators Of Lipid Synthesismentioning

confidence: 81%

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Lipid synthesis and membrane contact sites: a crossroads for cellular physiology

Fernández-Murray

McMaster

2016

Journal of Lipid Research

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high throughput analyses, makes this yeast a powerful organism to unveil the intricacies of this field. The yeast S. cerevisiae has played a foundational role in the field of molecular and cellular biology of lipids, including the identification of membrane contact sites (MCSs) and how they link lipid metabolism with organelle dynamics. We present advances in two topics where extensive and outstanding contributions have recently been made where their relevance transcends the yeast lipid field. We first review new information about the phosphatidic acid (PA) phosphatase, Pah1, the yeast homolog of human lipin, and its role in directing lipid flux into membrane synthesis or storage. We review the contribution of Pah1 to lipid droplet (LD) formation and its interaction with the seipin complex, Fld1/Ldb16, to regulate endoplasmic reticulum (ER)-LD contact site dynamics. Second, we recapitulate recent developments revealing MCS connections between the ER and mitochondria with other cellular compartments, and how these intersect with the maintenance of lipid homeostasis. Furthermore, we explore MCS redundancies that allow cells to cope with changing metabolic demand. PA METABOLISM CO-COORDINATES MEMBRANE AND LD SYNTHESISPA is the common precursor for the synthesis of membrane phospholipids (PLs) and the major component of The pervasive importance of lipids in cell biology has become evident. From structural roles defining cellular compartments and surfaces with specific biological properties to functional roles in signal transduction processes and modulation of regulatory networks, the involvement of lipids in varied cellular functions is well-established. Concurrently, we have gained a broad understanding about the repertoire of proteins involved in synthesis, degradation, transport, and sensing of lipids, as well as the regulatory mechanisms that interconnect lipid metabolism with other cellular processes. The amenability of Saccharomyces cerevisiae to classical approaches of molecular genetics, and toThe work on the science described in this review was supported by a Discovery Grant from the Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada to C.R.M. Manuscript received 19 July 2016 and in revised form 6 August 2016. Published, JLR Papers in Press, August 12, 2016 DOI 10.1194 Lipid synthesis and membrane contact sites: a crossroads for cellular physiology Abbreviations: cER, cortical endoplasmic reticulum; ChiMERA, construct helping in mitochondria-endoplasmic reticulum association; CL, cardiolipin; DAG, diacylglycerol; EMC, endoplasmic reticulum membrane protein complex; ER, endoplasmic reticulum; ERMES, endoplasmic reticulum-mitochondria encounter structure; HOPS, homotypic fusion and vacuole protein sorting; Lam, lipid transfer protein anchored at a membrane contact site; LD, lipid droplet; Ltc, lipid transfer at contact site; LTP, lipid transfer protein; Mcp, maintenance of mitochondrial morphology 10 complementing protein; M...

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Section: Pa Directly Binds Transcriptional Regulators Of Lipid Synthesismentioning

confidence: 81%

“…The physiological relevance of Pah1 has been uncovered by studying pah1 yeast strains (9,14,22,(39)(40)(41). The absence of Pah1 leads to elevated levels of PA and other PLs, which is thought to cause the observed hyperproliferation of the nuclear ER (10,11,36).…”

Section: Pa Directly Binds Transcriptional Regulators Of Lipid Synthesismentioning

confidence: 99%

Lipid synthesis and membrane contact sites: a crossroads for cellular physiology

Fernández-Murray

McMaster

2016

Journal of Lipid Research

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“…respiratory deficiency) (1,22) or at elevated temperatures (1,17,22) and exhibit defects in cell wall integrity (23,24) and vacuole fusion (e.g. as related to protein trafficking) (25). With respect to mammalian cell physiology, defects in lipin PAP enzymes result in metabolic disorders that include lipodystrophy, insulin resistance, peripheral neuropathy, rhabdomyolysis, and inflammation (2, 26 -37).…”

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confidence: 99%

Phosphorylation Regulates the Ubiquitin-independent Degradation of Yeast Pah1 Phosphatidate Phosphatase by the 20S Proteasome

Hsieh

Han

et al. 2015

Journal of Biological Chemistry

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Background: Yeast Pah1 phosphatidate phosphatase required for triacylglycerol synthesis is subject to proteasome-mediated degradation. Results: Pah1 is degraded by the 20S proteasome in a ubiquitin-independent manner that is governed by its phosphorylation state. Conclusion: 20S proteasomal degradation of Pah1 is regulated by phosphorylation and dephosphorylation. Significance: Pah1 function in lipid metabolism is regulated by the 20S proteasome.

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“…Differential effects of N-ethylmaleimide on Lpp1p (sensitive to inhibition) and Dpp1p (insensitive to inhibition) PAP activities might also be used to differentiate these Mg 2ϩ -independent enzymes in yeast extracts (36,41), yet the sensitivity to N-ethylmaleimide inhibition cannot be used to differentiate Mg 2ϩ -dependent and Mg 2ϩ -independent PAP activities in yeast. Likewise, inhibition by propranolol, a nonspecific ␤-blocker (80) that is commonly used to establish roles of PAP enzymes in various physiological processes (63,103,104), cannot be used to distinguish between App1p and Pah1p PAP enzymes or to distinguish between Mg 2ϩ -dependent and Mg 2ϩ -independent PAP enzymes because these PAP enzymes are sensitive to this reagent (41, 77,82,105).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Yeast Actin Patch Protein App1p Phosphatidate Phosphatase

Chae

Carman

2013

Journal of Biological Chemistry

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Background: Yeast App1p is a phosphatidate phosphatase (PAP) that interacts with endocytic proteins at cortical actin patches. Results: App1p PAP was purified from yeast and characterized with respect to its enzymological, kinetic, and regulatory properties. Conclusion: App1p PAP exhibits similar, but also distinct properties from other PAP enzymes. Significance: App1p PAP may regulate the balance of phosphatidate and diacylglycerol for endocytosis.

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Yeast Lipin 1 Orthologue Pah1p Regulates Vacuole Homeostasis and Membrane Fusion

Cited by 93 publications

References 80 publications

Lipid synthesis and membrane contact sites: a crossroads for cellular physiology

Lipid synthesis and membrane contact sites: a crossroads for cellular physiology

Phosphorylation Regulates the Ubiquitin-independent Degradation of Yeast Pah1 Phosphatidate Phosphatase by the 20S Proteasome

Characterization of the Yeast Actin Patch Protein App1p Phosphatidate Phosphatase

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