Intramitochondrial transfer of phospholipids in the yeast, Saccharomyces cerevisiae.

Simbeni, Renate; Paltauf, Fritz; Daum, Günther

doi:10.1016/s0021-9258(19)40227-5

Cited by 73 publications

(9 citation statements)

References 24 publications

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“…This includes MDM10 and MMM1 , which were originally identifi ed as genes required for mitochondrial inheritance and DNA stability ( Boldogh et al, 1998 ) In agreement with an inhibitory role of Gep1 for PE export from mitochondria, we observed in the absence of Gep1 a slight increase of PC, which is generated by methyl transferases in ER membranes using mitochondrial PE ( Kodaki and Yamashita, 1989 ). Contact sites between inner and outer mitochondrial membranes have been discussed as sites of phospholipid transport ( Simbeni et al, 1990 ). It will be therefore of interest to examine whether Gep1-like proteins locate to these sites.…”

Section: Discussionsupporting

confidence: 79%

“…It is therefore conceivable that defi ned lipid clusters with specifi c functions exist in the inner membrane of mitochondria. Contact sites between inner and outer mitochondrial membrane, at which import of nuclear-encoded mitochondrial proteins occurs ( Reichert and Neupert, 2002 ) and which have been linked to phospholipid transport processes ( Simbeni et al, 1990 ), were found to be enriched in PE and CL, and may represent such specialized membrane domains. Ringlike prohibitin complexes may serve as membrane organizers and affect the distribution of CL and PE in the membrane bilayer ( Fig.…”

Section: Discussionmentioning

confidence: 99%

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The genetic interactome of prohibitins: coordinated control of cardiolipin and phosphatidylethanolamine by conserved regulators in mitochondria

Osman

Haag

Potting

et al. 2009

Journal of Cell Biology

268

337

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Prohibitin ring complexes in the mitochondrial inner membrane regulate cell proliferation as well as the dynamics and function of mitochondria. Although prohibitins are essential in higher eukaryotes, prohibitin-deficient yeast cells are viable and exhibit a reduced replicative life span. Here, we define the genetic interactome of prohibitins in yeast using synthetic genetic arrays, and identify 35 genetic interactors of prohibitins (GEP genes) required for cell survival in the absence of prohibitins. Proteins encoded by these genes include members of a conserved protein family, Ups1 and Gep1, which affect the processing of the dynamin-like GTPase Mgm1 and thereby modulate cristae morphogenesis. We show that Ups1 and Gep1 regulate the levels of cardiolipin and phosphatidylethanolamine in mitochondria in a lipid-specific but coordinated manner. Lipid profiling by mass spectrometry of GEP-deficient mitochondria reveals a critical role of cardiolipin and phosphatidylethanolamine for survival of prohibitin-deficient cells. We propose that prohibitins control inner membrane organization and integrity by acting as protein and lipid scaffolds.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

The genetic interactome of prohibitins: coordinated control of cardiolipin and phosphatidylethanolamine by conserved regulators in mitochondria

Osman

Haag

Potting

et al. 2009

Journal of Cell Biology

268

337

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“…Several lines of evidence suggest that lipid exchange between the OM and IM occurs at contact sites (Simbeni et al, 1990). CL binding may recruit Ups2-Mdm35 to these sites, which are enriched in CL (Simbeni et al, 1991;Connerth et al, 2012).…”

Section: Deletion Of Ups2 Preserves Respiratory Growth and Cristae Morphology In The Absence Of Mic Os Subunitsmentioning

confidence: 99%

“…PE can be synthesized within mitochondria through decarboxylation of ER-derived PS by Psd1, which is located in the IM and exposes its catalytic domain to the IMS (Choi et al, 2005;Horvath et al, 2012). A fraction of PE is exported from mitochondria, transferred to the ER, and converted to PC, an abundant phospholipid in cellular membranes (Simbeni et al, 1990;Birner et al, 2001). Thus, mitochondrial PE synthesis is of pivotal importance for the lipid homeostasis of mitochondrial and other cellular membranes.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, mitochondrial PE synthesis is of pivotal importance for the lipid homeostasis of mitochondrial and other cellular membranes. However, it remained unclear how Ups2-Mdm35 complexes affected the accumulation of mitochondrial PE, as the activity of Psd1 and the synthesis of PC were not affected in ups2Δ cells (Osman et al, 2009;Tamura et al, 2012a) and the requirement of intermembrane space proteins for PS trafficking was questioned (Simbeni et al, 1990;Tamura et al, 2012b). Here, we identify Ups2-Mdm35 as PS-specific lipid transfer proteins and unravel an unexpected role of mitochondrial contact sites stabilized by MIC OS for mitochondrial PE synthesis.…”

Section: Introductionmentioning

confidence: 99%

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MICOS and phospholipid transfer by Ups2–Mdm35 organize membrane lipid synthesis in mitochondria

Aaltonen

Friedman

Osman

et al. 2016

Journal of Cell Biology

143

163

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Mitochondria exert critical functions in cellular lipid metabolism and promote the synthesis of major constituents of cellular membranes, such as phosphatidylethanolamine (PE) and phosphatidylcholine. Here, we demonstrate that the phosphatidylserine decarboxylase Psd1, located in the inner mitochondrial membrane, promotes mitochondrial PE synthesis via two pathways. First, Ups2-Mdm35 complexes (SLMO2-TRI AP1 in humans) serve as phosphatidylserine (PS)-specific lipid transfer proteins in the mitochondrial intermembrane space, allowing formation of PE by Psd1 in the inner membrane. Second, Psd1 decarboxylates PS in the outer membrane in trans, independently of PS transfer by Ups2-Mdm35. This latter pathway requires close apposition between both mitochondrial membranes and the mitochondrial contact site and cristae organizing system (MIC OS). In MIC OS-deficient cells, limiting PS transfer by Ups2-Mdm35 and reducing mitochondrial PE accumulation preserves mitochondrial respiration and cristae formation. These results link mitochondrial PE metabolism to MIC OS, combining functions in protein and lipid homeostasis to preserve mitochondrial structure and function.

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Phosphatidylserine decarboxylase downregulation in uric acid‑induced hepatic mitochondrial dysfunction and apoptosis

Liu

Huang

et al. 2023

MedComm

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The molecular mechanisms underlying uric acid (UA)‐induced mitochondrial dysfunction and apoptosis have not yet been elucidated. Herein, we investigated underlying mechanisms of UA in the development of mitochondrial dysfunction and apoptosis. We analyzed blood samples of individuals with normal UA levels and patients with hyperuricemia. Results showed that patients with hyperuricemia had significantly elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, which may indicate liver or mitochondrial damage in patients with hyperuricemia. Subsequently, lipidomic analysis of mouse liver tissue mitochondria and human liver L02 cell mitochondria was performed. Compared with control group levels, high UA increased mitochondrial phosphatidylserine (PS) and decreased mitochondrial phosphatidylethanolamine (PE) levels, whereas the expression of mitochondrial phosphatidylserine decarboxylase (PISD) that mediates PS and PE conversion was downregulated. High UA levels also inhibited signal transducer and activator of transcription 3 （STAT3） phosphorylation as well as mitochondrial respiration, while inducing apoptosis both in vivo and in vitro. Treatment with allopurinol, overexpression of PISD, and lyso‐PE (LPE) administration significantly attenuated the three above‐described effects in vitro. In conclusion, UA may induce mitochondrial dysfunction and apoptosis through mitochondrial PISD downregulation. This study provides a new perspective on liver damage caused by hyperuricemia.

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Intramitochondrial transfer of phospholipids in the yeast, Saccharomyces cerevisiae.

Cited by 73 publications

References 24 publications

The genetic interactome of prohibitins: coordinated control of cardiolipin and phosphatidylethanolamine by conserved regulators in mitochondria

The genetic interactome of prohibitins: coordinated control of cardiolipin and phosphatidylethanolamine by conserved regulators in mitochondria

MICOS and phospholipid transfer by Ups2–Mdm35 organize membrane lipid synthesis in mitochondria

Phosphatidylserine decarboxylase downregulation in uric acid‑induced hepatic mitochondrial dysfunction and apoptosis

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