scholarly journals Yeast homologs of human MCUR1 regulate mitochondrial proline metabolism

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohammad Zulkifli ◽  
John K. Neff ◽  
Shrishiv A. Timbalia ◽  
Natalie M. Garza ◽  
Yingqi Chen ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Redox Balance ◽  
Yeast Cells ◽  
Proline Metabolism ◽  
Inner Mitochondrial Membrane ◽  
Carbon And Nitrogen ◽  
Calcium Uniporter ◽  
Proline Utilization ◽  
Evolutionarily Conserved ◽  
Oligomeric Complex

Abstract Mitochondria house evolutionarily conserved pathways of carbon and nitrogen metabolism that drive cellular energy production. Mitochondrial bioenergetics is regulated by calcium uptake through the mitochondrial calcium uniporter (MCU), a multi-protein complex whose assembly in the inner mitochondrial membrane is facilitated by the scaffold factor MCUR1. Intriguingly, many fungi that lack MCU contain MCUR1 homologs, suggesting alternate functions. Herein, we characterize Saccharomyces cerevisiae homologs Put6 and Put7 of MCUR1 as regulators of mitochondrial proline metabolism. Put6 and Put7 are tethered to the inner mitochondrial membrane in a large hetero-oligomeric complex, whose abundance is regulated by proline. Loss of this complex perturbs mitochondrial proline homeostasis and cellular redox balance. Yeast cells lacking either Put6 or Put7 exhibit a pronounced defect in proline utilization, which can be corrected by the heterologous expression of human MCUR1. Our work uncovers an unexpected role of MCUR1 homologs in mitochondrial proline metabolism.

scholarly journals Inactivation of YME2/RNA12, which encodes an integral inner mitochondrial membrane protein, causes increased escape of DNA from mitochondria to the nucleus in Saccharomyces cerevisiae.

1996 ◽  
Vol 16 (6) ◽  
pp. 2764-2771 ◽  
Author(s):  
T Hanekamp ◽  
P E Thorsness
Keyword(s):  
Membrane Protein ◽  
Mitochondrial Membrane ◽  
Nuclear Gene ◽  
Genetic Interactions ◽  
Yeast Cells ◽  
Null Alleles ◽  
Growth Defect ◽  
Inner Mitochondrial Membrane ◽  
Synthetic Growth ◽  
Mitochondrial Membrane Protein

Inactivation of the yeast nuclear gene YMe2 causes an increased rate of DNA escape from mitochondria to the nucleus. Mutations in yme2 also show genetic interactions with yme1, a second gene that affects DNA escape from mitochondria to the nucleus. The yme1 cold-sensitive growth phenotype is suppressed by yme2 mutations. In addition, yme1 yme2 double mutants exhibit a synthetic growth defect on ethanol-glycerol medium at 30 degrees C. YME2 was isolated by complementation of the synthetic growth defect of yme1 yme2 strains and was found to be identical with the previously cloned RNA12 gene. The dominant temperature-sensitive mutation RNA12-1 prevents growth of yeast cells at 37 degrees C. YME2 encodes a protein with a predicted molecular weight of 96,681 and is an integral inner mitochondrial membrane protein. The larger carboxyl-terminal domain of the YME2 gene product faces the intermembrane space. Null alleles of yme2 display the same genetic interactions with yme1 and high rate of DNA escape from mitochondria as do the originally isolated yme2 mutant strains. Disruption of yme2 causes a strain-dependent growth defect on nonfermentable carbon sources.

scholarly journals Structure and reconstitution of a MCU-EMRE mitochondrial Ca2+ uniporter complex

2020 ◽  
Author(s):  
Chongyuan Wang ◽  
Rozbeh Baradaran ◽  
Stephen Barstow Long
Keyword(s):  
Mitochondrial Membrane ◽  
Transmembrane Domain ◽  
Functional Unit ◽  
Transmembrane Helix ◽  
Coiled Coil ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Calcium Uniporter ◽  
Calcium Uniporter ◽  
The Matrix ◽  
Ion Pore

AbstractThe proteins MCU and EMRE form the minimal functional unit of the mitochondrial calcium uniporter complex in metazoans, a highly selective and tightly controlled Ca2+ channel of the inner mitochondrial membrane that regulates cellular metabolism. Here we present functional reconstitution of an MCU-EMRE complex from the red flour beetle, Tribolium castaneum, and a cryo-EM structure of the complex at 3.5 Å resolution. Robust Ca2+ uptake is observed into proteoliposomes containing the purified complex and is dependent on EMRE. The structure reveals a tetrameric channel with a single ion pore. EMRE is located at the periphery of the transmembrane domain and associates primarily with the first transmembrane helix of MCU. Coiled coil and juxtamembrane domains within the matrix portion of the complex adopt markedly different conformations than in a structure of a human MCU-EMRE complex, suggesting that the structures represent different conformations of these functionally similar metazoan channels.

scholarly journals Asymmetrical distribution of cardiolipin in yeast inner mitochondrial membrane triggered by carbon catabolite repression

1997 ◽  
Vol 324 (2) ◽  
pp. 627-634 ◽  
Author(s):  
Paul François GALLET ◽  
Jean-Michel PETIT ◽  
Abderrahman MAFTAH ◽  
Alain ZACHOWSKI ◽  
Raymond JULIEN
Keyword(s):  
Mitochondrial Membrane ◽  
Carbon Catabolite Repression ◽  
Yeast Cells ◽  
Inner Mitochondrial Membrane ◽  
Outer Leaflet ◽  
Mitochondrial Inner Membrane ◽  
Membrane Topography ◽  
The Matrix ◽  
Fermentative Growth ◽  
Antibiotic Inhibition

Transmembrane asymmetry of cardiolipin in yeast was monitored during the switch from fermentative to gluconeogenic growth and the reverse. As soon as cells used ethanol as an electron donor to produce ATP by oxidative phosphorylation, rapid and abundant cardiolipin synthesis was observed on the matrix side of the inner mitochondrial membrane followed by a transverse rearrangement between the two leaflets. The cardiolipin distribution changed from about 20:80 (in/out) to 70:30 (in/out), and after translocation towards the outer leaflet it finally became 37:63 (in/out). At the same time, cytochrome coxidase activity remained stable, then increased as a possible result of the topographical rearrangement. During the reverse process from gluconeogenic to fermentative growth, the amount of cardiolipin rapidly decreased by half, its bilayer distribution apparently changing to a monolayer organization before the 20:80 (in/out) asymmetry of repressed cells was re-established. Experimental impairment of cardiolipin topography by antibiotic inhibition of gene expression or in situdissipation of mitochondrial membrane potential produced data that prove that the amount and transmembrane distribution of the phospholipid are two specific parameters of the mitochondrial inner membrane organization in both fermentative (2.2 fmol/cell and 20:80, in/out) and gluconeogenic (4.2 fmol/cell and 37:63, in/out) growing yeast cells. Finally, the inner mitochondrial membrane topography of cardiolipin appeared to be closely associated with the transmembrane redox potential.

scholarly journals The mechanism of MICU-dependent gating of the mitochondrial Ca2+uniporter

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Vivek Garg ◽  
Junji Suzuki ◽  
Ishan Paranjpe ◽  
Tiffany Unsulangi ◽  
Liron Boyman ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Comprehensive Analysis ◽  
Intermembrane Space ◽  
Inner Mitochondrial Membrane ◽  
Rigorous Analysis ◽  
Regulatory Subunits ◽  
Mitochondrial Calcium Uniporter ◽  
Isolated Mitochondria ◽  
Calcium Uniporter ◽  
Selective Channel

Ca2+ entry into mitochondria is through the mitochondrial calcium uniporter complex (MCUcx), a Ca2+-selective channel composed of five subunit types. Two MCUcx subunits (MCU and EMRE) span the inner mitochondrial membrane, while three Ca2+-regulatory subunits (MICU1, MICU2, and MICU3) reside in the intermembrane space. Here, we provide rigorous analysis of Ca2+ and Na+ fluxes via MCUcx in intact isolated mitochondria to understand the function of MICU subunits. We also perform direct patch clamp recordings of macroscopic and single MCUcx currents to gain further mechanistic insights. This comprehensive analysis shows that the MCUcx pore, composed of the EMRE and MCU subunits, is not occluded nor plugged by MICUs during the absence or presence of extramitochondrial Ca2+ as has been widely reported. Instead, MICUs potentiate activity of MCUcx as extramitochondrial Ca2+ is elevated. MICUs achieve this by modifying the gating properties of MCUcx allowing it to spend more time in the open state.

Modulation of the calcium-activated BK-channel of the inner mitochondrial membrane by hypoxia

2007 ◽  
Vol 34 (S 2) ◽  
Author(s):  
D Siemen ◽  
Y Cheng ◽  
X Gu ◽  
P Bednarczyk ◽  
GG Haddad ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Bk Channel ◽  
Inner Mitochondrial Membrane

The Efects of Spaceflight on Mitochondria in Human Lymphocytes (Jurkat).

1999 ◽  
Vol 5 (S2) ◽  
pp. 1118-1119
Author(s):  
Heide Schatten ◽  
Marian Lewis
Keyword(s):  
Mitochondrial Membrane ◽  
Space Shuttle ◽  
Human Lymphocytes ◽  
Jurkat Cells ◽  
Apoptotic Bodies ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Alterations ◽  
Mitochondrial Volume ◽  
Number Of Cells ◽  
Related Increase

Spaceflight induced mitochondrial alterations have been reported for muscle and may be associated with altered physiological functions in space. Mitochondrial alterations are also indicative of preapoptotic events which are seen in greater amounts in cells exposed to spaceflight when compared with cells cultured at 1 g. Preapoptotic mitochondrial changes include alterations of processes at the inner mitochondrial membrane and can result in changes in mitochondrial volume. Higher amounts of oxidative stress during space flight may be one of the causes for changes which lead to apoptosis. Jurkat cells flown on the STS-76 space shuttle mission showed an increase in the number of cells with apoptotic bodies early in the mission and a time-dependent, microgravity-related increase in the Fas/APO-1 cell death factor. Here we investigated the morphology of mitochondria in Jurkat cells exposed to spaceflight during the STS-76 mission.

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