The conserved GTPase Gem1 regulates endoplasmic reticulum–mitochondria connections

Kornmann, Benoı̂t; Osman, Christof; Walter, Peter

doi:10.1073/pnas.1111314108

Cited by 314 publications

(351 citation statements)

References 32 publications

Supporting

Mentioning

321

Contrasting

Unclassified

Order By: Relevance

“…Consistent with a role for ERMES proteins in maintaining ER-mitochondrial contacts, phospholipids exchange between the ER and mitochondria was found to slow in cells missing any one of the ERMES proteins (Kornmann et al, 2009). A role for the ERMES complex in mitochondrial lipid homeostasis is also suggested by the genetic interaction of genes encoding ERMES proteins and those required for cardiolipin (CL) biosynthesis (Kornmann et al, 2011), which occurs in mitochondria. However, the role of ERMES in lipid exchange between the ER and mitochondria remains unclear; a recent study found little or no decrease in the transfer of phosphatidylserine (PS) in cells missing ERMES proteins (Nguyen et al, 2012).…”

Section: Introductionmentioning

confidence: 67%

ER-shaping proteins facilitate lipid exchange between the ER and mitochondria in S. cerevisiae

Voss

Lahiri

Young

et al. 2012

Journal of Cell Science

106

View full text Add to dashboard Cite

SummaryThe endoplasmic reticulum (ER) forms a network of sheets and tubules that extends throughout the cell. Proteins required to maintain this complex structure include the reticulons, reticulon-like proteins, and dynamin-like GTPases called atlastins in mammals and Sey1p in Saccharomyces cerevisiae. Yeast cells missing these proteins have abnormal ER structure, particularly defects in the formation of ER tubules, but grow about as well as wild-type cells. We screened for mutations that cause cells that have defects in maintaining ER tubules to grow poorly. Among the genes we found were members of the ER mitochondria encounter structure (ERMES) complex that tethers the ER and mitochondria. Close contacts between the ER and mitochondria are thought to be sites where lipids are moved from the ER to mitochondria, a process that is required for mitochondrial membrane biogenesis. We show that ER to mitochondria phospholipid transfer slows significantly in cells missing both ER-shaping proteins and the ERMES complex. These cells also have altered steady-state levels of phospholipids. We found that the defect in ER to mitochondria phospholipid transfer in a strain missing ER-shaping proteins and a component of the ERMES complex was corrected by expression of a protein that artificially tethers the ER and mitochondria. Our findings indicate that ER-shaping proteins play a role in maintaining functional contacts between the ER and mitochondria and suggest that the shape of the ER at ER-mitochondria contact sites affects lipid exchange between these organelles.

show abstract

Section: Introductionmentioning

confidence: 67%

ER-shaping proteins facilitate lipid exchange between the ER and mitochondria in S. cerevisiae

Voss

Lahiri

Young

et al. 2012

Journal of Cell Science

106

View full text Add to dashboard Cite

show abstract

“…Mammalian MAMs are formed by protein tethers, similar to the tetrameric tethering complexes in fungi known as ER-mitochondria encounter structures (ERMES) (Kornmann et al, 2009). However, of the more than 30 proteins involved in vertebrate MAM function, only two of them, GRAMD1A, which corresponds to yeast Lam6p, and MIRO (also known as RHOT1), which corresponds to yeast Gem1p, are conserved in ERMES (Kornmann et al, 2011;Elbaz-Alon et al, 2015). This increased complexity of animal MAMs suggests they acquired new roles beyond those controlled by ERMES (HerreraCruz and Simmen, 2017).…”

Section: Introductionmentioning

confidence: 99%

Caught in the act – protein adaptation and the expanding roles of the PACS proteins in tissue homeostasis and disease

Thomas

Aslan

Thomas

et al. 2017

Journal of Cell Science

View full text Add to dashboard Cite

Vertebrate proteins that fulfill multiple and seemingly disparate functions are increasingly recognized as vital solutions to maintaining homeostasis in the face of the complex cell and tissue physiology of higher metazoans. However, the molecular adaptations that underpin this increased functionality remain elusive. In this Commentary, we review the PACS proteins -which first appeared in lower metazoans as protein traffic modulators and evolved in vertebrates to integrate cytoplasmic protein traffic and interorganellar communication with nuclear gene expression -as examples of protein adaptation 'caught in the act'. Vertebrate PACS-1 and PACS-2 increased their functional density and roles as metabolic switches by acquiring phosphorylation sites and nuclear trafficking signals within disordered regions of the proteins. These findings illustrate one mechanism by which vertebrates accommodate their complex cell physiology with a limited set of proteins. We will also highlight how pathogenic viruses exploit the PACS sorting pathways as well as recent studies on PACS genes with mutations or altered expression that result in diverse diseases. These discoveries suggest that investigation of the evolving PACS protein family provides a rich opportunity for insight into vertebrate cell and organ homeostasis.

show abstract

“…The mechanism underlying this Ca 2 þ -dependent regulation is unclear [7,8]. The GTPase domains of Miro influence mitochondrial morphology [1,4], and both EF hand and GTPase domains regulate endoplasmic reticulum-mitochondrial connections [9,10]. Miro is also a common substrate of the two Parkinson's disease-related proteins Pink1 kinase and Parkin E3 ubiquitin ligase in a signalling cascade that facilitates mitochondrial degradation [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Structural coupling of the EF hand and C‐terminal GTPase domains in the mitochondrial protein Miro

et al. 2013

View full text Add to dashboard Cite

Miro is a highly conserved calcium-binding GTPase at the regulatory nexus of mitochondrial transport and autophagy. Here we present crystal structures comprising the tandem EF hand and carboxy terminal GTPase (cGTPase) domains of Drosophila Miro. The structures reveal two previously unidentified 'hidden' EF hands, each paired with a canonical EF hand. Each EF hand pair is bound to a helix that structurally mimics an EF hand ligand. A key nucleotide-sensing element and a Pink1 phosphorylation site both lie within an extensive EF hand-cGTPase interface. Our results indicate structural mechanisms for calcium, nucleotide and phosphorylation-dependent regulation of mitochondrial function by Miro.

show abstract

The conserved GTPase Gem1 regulates endoplasmic reticulum–mitochondria connections

Cited by 314 publications

References 32 publications

ER-shaping proteins facilitate lipid exchange between the ER and mitochondria in S. cerevisiae

ER-shaping proteins facilitate lipid exchange between the ER and mitochondria in S. cerevisiae

Caught in the act – protein adaptation and the expanding roles of the PACS proteins in tissue homeostasis and disease

Structural coupling of the EF hand and C‐terminal GTPase domains in the mitochondrial protein Miro

Contact Info

Product

Resources

About