MAM (mitochondria-associated membranes) in mammalian cells: Lipids and beyond

Vance, Jean E.

doi:10.1016/j.bbalip.2013.11.014

Cited by 521 publications

(522 citation statements)

References 195 publications

Supporting

Mentioning

504

Contrasting

Unclassified

Order By: Relevance

“…While most of these domains are found in the plasma membrane, intracellular lipid rafts have also been described (Browman et al , 2006). One of these intracellular lipid rafts is called mitochondria‐associated ER membranes (MAM), a functional subdomain of the ER located in close apposition to mitochondria that regulates key cellular metabolic functions (Vance, 2014). …”

Section: Introductionmentioning

confidence: 99%

Increased localization of APP‐C99 in mitochondria‐associated ER membranes causes mitochondrial dysfunction in Alzheimer disease

et al. 2017

View full text Add to dashboard Cite

In the amyloidogenic pathway associated with Alzheimer disease (AD), the amyloid precursor protein (APP) is cleaved by β‐secretase to generate a 99‐aa C‐terminal fragment (C99) that is then cleaved by γ‐secretase to generate the β‐amyloid (Aβ) found in senile plaques. In previous reports, we and others have shown that γ‐secretase activity is enriched in mitochondria‐associated endoplasmic reticulum (ER) membranes (MAM) and that ER–mitochondrial connectivity and MAM function are upregulated in AD. We now show that C99, in addition to its localization in endosomes, can also be found in MAM, where it is normally processed rapidly by γ‐secretase. In cell models of AD, however, the concentration of unprocessed C99 increases in MAM regions, resulting in elevated sphingolipid turnover and an altered lipid composition of both MAM and mitochondrial membranes. In turn, this change in mitochondrial membrane composition interferes with the proper assembly and activity of mitochondrial respiratory supercomplexes, thereby likely contributing to the bioenergetic defects characteristic of AD.

show abstract

Section: Introductionmentioning

confidence: 99%

Increased localization of APP‐C99 in mitochondria‐associated ER membranes causes mitochondrial dysfunction in Alzheimer disease

et al. 2017

View full text Add to dashboard Cite

show abstract

“…52 In mammals, lipid transfer occurs also between mitochondria and the ER, at the sites of contact between these organelles. 15,53,54 Here the lipid-MERC serves as a platform for lipid biosynthesis, as demonstrated by Jane Vance. 10,14 At the MAM, phosphatidylserine is first synthesized in the ER by PSS1 and PSS2; then transferred to the mitochondrion, where a decarboxylase converts it to phosphatidylethanolamine; the latter is transferred back to the ER, where a methyltransferase, phosphatidylethanolamine N-methyltransferase-2, converts it into phosphatidylcholine, a major component of the cell membrane.…”

Section: The Lipid-merc: a Site Of Phospholipid Biosynthesis And Trafmentioning

confidence: 99%

“…[15][16][17][18] Although many papers have explored their function, only few have analyzed in details their structure, number and length. However, importantly, little attention has been given to the thickness of the MERC; that is, the width of the cleft separating the ER from the OMM.…”

Section: +mentioning

confidence: 99%

“…[10][11][12][13][14][15] MERCs and MAMs are sometime used as synonyms, but they do not mean the same thing. The term MERC describes the architecture and ultrastructural organization of the site of contact between the two organelles, which can be visualized by EM and that provide the physical platform for the execution of specific cellular functions.…”

Section: Introduction: Of Mercs and Mamsmentioning

confidence: 99%

See 1 more Smart Citation

The coming of age of the mitochondria–ER contact: a matter of thickness

2016

View full text Add to dashboard Cite

The sites of near-contact between the mitochondrion and the endoplasmic reticulum (ER) have earned a lot of attention due to their key role in the maintenance of lipid and calcium (Ca 2+ ) homeostasis, in the initiation of autophagy and mitochondrial division, and in sensing metabolic shifts. At these sites, typically called MAMs (mitochondria-associated ER membranes) or MERCs (mitochondria-ER contacts), the organelles juxtapose at a distance that can range from~10 to~50 nm. The multifunctional role of this subcellular compartment is puzzling; further, recent studies have shown that mitochondria-ER contacts are highly plastic structures that remodel upon metabolic transitions and that their activity in controlling lipid homeostasis could be involved in Alzheimer's disease pathogenesis. This review aims at integrating the functions of this subcellular compartment to its most characterizing and unexplored structural parameter, their 'thickness': that is, the width of the cleft that separates the cytosolic face of the outer mitochondrial membrane from that of the ER. We describe and discuss the reasons why the thickness of a MERC should be considered a regulated structural parameter of the cell that defines and controls its function. Further, we propose a MERC classification that will help organize the expanding field of MERCs biology and of their role in cell physiology and human disease.

show abstract

“…It has been shown that Gem1p functions to maintain mitochondrial morphology, retain mitochondrial DNA nucleoids, and promote mitochondrial inheritance in yeast (Frederick et al, 2004). Vance (2014) reports that the contact sites between mitochondria and the ER are hubs for lipid translocation and Ca 2+ traffic between the ER and mitochondria. The endoplasmic reticulummitochondria encounter structure (ERMES) forms a junction between mitochondria and the endoplasmic reticulum (ER).…”

Section: Rnai Etbr Sensitive Genes (Gem1 (Miro-1 or Rhot1))mentioning

confidence: 99%

Investigation of yeast genes possibly involved in mtDNA stability using the nematode Caenorhabditis elegans

Addo¹,

Cossard²,

Pichard³

et al. 2016

Afr. J. Biotechnol.

View full text Add to dashboard Cite

Screening of Caenorhabditis elegans genes possibly involved in the mitochondrial genome maintenance was performed using our previous validated method of RNAi combined with ethidium bromide. This was to knock down C. elegans genes homologous to yeast genes known to be involved in mtDNA stability but of unknown molecular function or to identify transient components that could play important role on the stability of mtDNA in a temporal and/or spatial manner. C. elegans homologs for 11 genes among 27 yeast genes for which deletion leads to a rho0 state were found, however, only 5 genes were present in the RNAi library. Out of these 5 genes, 1 gene (homolog of GEM1) gave a clear L3 arrest on RNAi and ethidium bromide indicating its involvement on mtDNA stability. Four other genes homologs of MTG2, YER087W, AVL9 and RRG3 did not lead to L3 arrest even though their deletion in Saccharomyces cerevisiae leads to rho0 state. Although MTG2 has been reported to be important in the function and structure on mtDNA stability in yeast, our results did not support those findings in C. elegans. The human homolog of this gene (MIRO1) can be considered as a candidate gene involved in mtDNA stability and sequenced in patients with mtDNA depletion diseases.

show abstract

MAM (mitochondria-associated membranes) in mammalian cells: Lipids and beyond

Cited by 521 publications

References 195 publications

Increased localization of APP‐C99 in mitochondria‐associated ER membranes causes mitochondrial dysfunction in Alzheimer disease

Increased localization of APP‐C99 in mitochondria‐associated ER membranes causes mitochondrial dysfunction in Alzheimer disease

The coming of age of the mitochondria–ER contact: a matter of thickness

Investigation of yeast genes possibly involved in mtDNA stability using the nematode Caenorhabditis elegans

Contact Info

Product

Resources

About