Research Progress in Mitochondria-associated Endoplasmic Reticulum Membrane and Its Application in Treatment of Diseases_Journal of Biomedical Engineering

Authors：

WUSiyuan ,  LIUXiaojing

Lab of Cardiovascular Diseases,Regenerative Medicine Research Center,West China Hospital,Sichuan University,Chengdu 610041,China;

Corresponding author：

LIUXiaojing, Email: liuxq@scu.edu.cn

Keywords：

mitochondria-associated endoplasmic reticulum membranes; mitochondria; endoplasmic reticulum; Ca²⁺ signaling

DOI：

10.7507/1001-5515.20160066

Video：

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Abstract Full text Figures/Tables Video References Cited by

The endoplasmic reticulum (ER) is physically connected to mitochondria through the specific sub-domain,called mitochondria-associated endoplasmic reticulum membranes (MAMs). These contacts are involved in calcium signaling,lipid transferring,mitochondrial fission and fusion and energy metabolism. Recently,MAMs alterations have been identified to associate with some diseases,including neurodegenerative diseases,obesity,cardiovascular diseases and cancer. Therefore,in this paper,we introduce the structure,function and detection methods of MAMs. Besides,we also summarize the potential role of MAMs in these diseases. In any case,the signaling at the MAMs might be a promising pharmacological target for several diseases.

Citation： WUSiyuan, LIUXiaojing. Research Progress in Mitochondria-associated Endoplasmic Reticulum Membrane and Its Application in Treatment of Diseases. Journal of Biomedical Engineering, 2016, 33(2): 388-393. doi: 10.7507/1001-5515.20160066 Copy

1.	MARCHI S,PATERGNANI S,PINTON P. The endoplasmic reticulum-mitochondria connection:one touch,multiple functions[J]. Biochim Biophys Acta,2014,1837(4):461-469.
2.	VANCE J E. Phospholipid synthesis in a membrane fraction associated with mitochondria[J]. J Biol Chem,1990,265(13):7248-7256.
3.	LÓPEZ-CRISOSTO C,BRAVO-SAGUA R,RODRIGUEZ-PEÑA M,et al. ER-to-mitochondria miscommunication and metabolic diseases[J]. Biochim Biophys Acta,2015,1852(10 Pt A):2096-2105.
4.	TUBBS E,THEUREY P,VIAL G,et al. Mitochondria-associated endoplasmic reticulum membrane (MAM) integrity is required for insulin signaling and is implicated in hepatic insulin resistance[J]. Diabetes,2014,63(10):3279-3294.
5.	GIORGI C,MISSIROLI S,PATERGNANI S,et al. Mitochondria-associated membranes:composition,molecular mechanisms,and physiopathological implications[J]. Antioxid Redox Signal,2015,22(12):995-1019.
6.	VAN VLIET A R,VERFAILLIE T,AGOSTINIS P. New functions of mitochondria associated membranes in cellular signaling[J]. Biochim Biophys Acta,2014,1843(10):2253-2262.
7.	AREA-GOMEZ E. Assessing the function of mitochondria-associated ER membranes[J]. Methods Enzymol,2014,547:181-197.
8.	WIECKOWSKI M R,GIORGI C,LEBIEDZINSKA M,et al. Isolation of mitochondria-associated membranes and mitochondria from animal tissues and cells[J]. Nat Protoc,2009,4(11):1582-1590.
9.	PAILLARD M,TUBBS E,THIEBAUT P A,et al. Depressing mitochondria-reticulum interactions protects cardiomyocytes from lethal hypoxia-reoxygenation injury[J]. Circulation,2013,128(14):1555-1565.
10.	BONONI A,BONORA M,MARCHI S,et al. Identification of PTEN at the ER and MAMs and its regulation of Ca(2+) signaling and apoptosis in a protein phosphatase-dependent manner[J]. Cell Death Differ,2013,20(12):1631-1643.
11.	SUGIURA A,NAGASHIMA Shun,TOKUYAMA T,et al. MITOL regulates endoplasmic reticulum-mitochondria contacts via Mitofusin2[J]. Mol Cell,2013,51(1):20-34.
12.	VANCE J E. Phospholipid synthesis and transport in mammalian cells[J]. Traffic,2015,16(1):1-18.
13.	NAON D,SCORRANO L. At the right distance:ER-mitochondria juxtaposition in cell Life and death[J]. Biochim Biophys Acta,2014,1843(10):2184-2194.
14.	LIU Z,LV Y,ZHAO N,et al. Protein kinase R-like ER kinase and its role in endoplasmic reticulum stress-decided cell fate[J]. Cell Death Dis,2015,6:e1822.
15.	NGOH G A,PAPANICOLAOU K N,WALSH K. Loss of mitofusin 2 promotes endoplasmic reticulum stress[J]. J Biol Chem,2012,287(24):20321-20332.
16.	MORI T,HAYASHI T,HAYASHI E,et al. Sigma-1 receptor chaperone at the ER-mitochondrion interface mediates the mitochondrion-ER-nucleus signaling for cellular survival[J]. PLoS One,2013,8(10):e76941.
17.	MATSUZAKI H,FUJIMOTO T,TANAKA M,et al. Tespa1 is a novel component of mitochondria-associated endoplasmic reticulum membranes and affects mitochondrial calcium flux[J]. Biochem Biophys Res Commun,2013,433(3):322-326.
18.	BRAVO R,VICENCIO J M,PARRA V,et al. Increased ER-mitochondrial coupling promotes mitochondrial respiration and bioenergetics during early phases of ER stress[J]. J Cell Sci,2011,124(Pt 13):2143-2152.
19.	ARRUDA A P,PERS B M,PARLAKGVL G,et al. Chronic enrichment of hepatic endoplasmic reticulum-mitochondria contact leads to mitochondrial dysfunction in obesity[J]. Nat Med,2014,20(12):1427-1435.
20.	REALI V,MEHDAWY B,NARDACCI R,et al. Reticulon protein-1C is a key component of MAMs[J]. Biochim Biophys Acta,2015,1853(3):733-745.
21.	YOKOSUKA T,GOTO H,FUJII H,et al. Flow cytometric chemosensitivity assay using JC-1,a sensor of mitochondrial transmembrane potential,in acute leukemia[J]. Cancer Chemother Pharmacol,2013,72(6):1335-1342.
22.	MIKHED Y,DAIBER A,STEVEN S. Mitochondrial oxidative stress,mitochondrial DNA damage and their role in age-related vascular dysfunction[J]. Int J Mol Sci,2015,16(7):15918-15953.
23.	VANCE J E. MAM (mitochondria-associated membranes) in mammalian cells:lipids and beyond[J]. Biochim Biophys Acta,2014,1841(4):595-609.
24.	VOLGYI K,JUHÁSZ G,KOVACS Z,et al. Dysfunction of endoplasmic reticulum (ER) and mitochondria (MT) in alzheimer's disease:the role of the ER-MT Cross-Talk[J]. Curr Alzheimer Res,2015,12(7):655-672.
25.	SCHREINER B,HEDSKOG L,WIEHAGER B,et al. Amyloid-β peptides are generated in mitochondria-associated endoplasmic reticulum membranes[J]. J Alzheimers Dis,2015,43(2):369-374.
26.	GUARDIA-LAGUARTA C,AREA-GOMEZ E,SCHON E A,et al. A new role for α-synuclein in Parkinson's disease:Alteration of ER-mitochondrial communication[J]. Mov Disord,2015,30(8):1026-1033.
27.	CALÌ T,OTTOLINI D,NEGRO A,et al. α-Synuclein controls mitochondrial Calcium homeostasis by enhancing endoplasmic reticulum-mitochondria interactions[J]. J Biol Chem,2012,287(22):17914-17929.
28.	PEINADO J R,DIAZ-RUIZ A,FR? HBECK G,et al. Mitochondria in metabolic disease:getting clues from proteomic studies[J]. Proteomics,2014,14(4/5):452-466.
29.	CNOP M,FOUFELLE F,VELLOSO L A. Endoplasmic reticulum stress,obesity and diabetes[J]. Trends Mol Med,2012,18(1):59-68.
30.	YUZEFOVYCH L V,MUSIYENKO S I,WILSON G L,et al. Mitochondrial DNA damage and dysfunction,and oxidative stress are associated with endoplasmic reticulum stress,protein degradation and apoptosis in high fat diet-induced insulin resistance mice[J]. PLoS One,2013,8(1):e54059.
31.	SCHNEEBERGER M,DIETRICH M O,SEBASTIÁN D,et al. Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance[J]. Cell,2013,155(1):172-187.
32.	GUTIÉRREZ T,PARRA V,TRONCOSO R,et al. Alteration in mitochondrial Ca(2+) uptake disrupts insulin signaling in hypertrophic cardiomyocytes[J]. Cell Commun Signal,2014,12:68.
33.	BETZ C,STRACKA D,PRESCIANOTTO-BASCHONG C,et al. Feature article:mTOR complex 2-Akt signaling at mitochondria-associated endoplasmic reticulum membranes (MAM) regulates mitochondrial physiology[J]. Proc Natl Acad Sci U S A,2013,110(31):12526-12534.
34.	CERQUA C,ANESTI V,PYAKUREL A,et al. Trichoplein/mitostatin regulates endoplasmic reticulum-mitochondria juxtaposition[J]. EMBO Rep,2010,11(11):854-860.
35.	MARTIN L J,LAU E,SINGH H,et al. ABCC6 localizes to the mitochondria-associated membrane[J]. Circ Res,2012,111(5):516-520.
36.	SUTENDRA G,DROMPARIS P,WRIGHT P,et al. The role of Nogo and the mitochondria-endoplasmic reticulum unit in pulmonary hypertension[J]. Sci Transl Med,2011,3(88):88ra55.

1. MARCHI S,PATERGNANI S,PINTON P. The endoplasmic reticulum-mitochondria connection:one touch,multiple functions[J]. Biochim Biophys Acta,2014,1837(4):461-469.
2. VANCE J E. Phospholipid synthesis in a membrane fraction associated with mitochondria[J]. J Biol Chem,1990,265(13):7248-7256.
3. LÓPEZ-CRISOSTO C,BRAVO-SAGUA R,RODRIGUEZ-PEÑA M,et al. ER-to-mitochondria miscommunication and metabolic diseases[J]. Biochim Biophys Acta,2015,1852(10 Pt A):2096-2105.
4. TUBBS E,THEUREY P,VIAL G,et al. Mitochondria-associated endoplasmic reticulum membrane (MAM) integrity is required for insulin signaling and is implicated in hepatic insulin resistance[J]. Diabetes,2014,63(10):3279-3294.
5. GIORGI C,MISSIROLI S,PATERGNANI S,et al. Mitochondria-associated membranes:composition,molecular mechanisms,and physiopathological implications[J]. Antioxid Redox Signal,2015,22(12):995-1019.
6. VAN VLIET A R,VERFAILLIE T,AGOSTINIS P. New functions of mitochondria associated membranes in cellular signaling[J]. Biochim Biophys Acta,2014,1843(10):2253-2262.
7. AREA-GOMEZ E. Assessing the function of mitochondria-associated ER membranes[J]. Methods Enzymol,2014,547:181-197.
8. WIECKOWSKI M R,GIORGI C,LEBIEDZINSKA M,et al. Isolation of mitochondria-associated membranes and mitochondria from animal tissues and cells[J]. Nat Protoc,2009,4(11):1582-1590.
9. PAILLARD M,TUBBS E,THIEBAUT P A,et al. Depressing mitochondria-reticulum interactions protects cardiomyocytes from lethal hypoxia-reoxygenation injury[J]. Circulation,2013,128(14):1555-1565.
10. BONONI A,BONORA M,MARCHI S,et al. Identification of PTEN at the ER and MAMs and its regulation of Ca(2+) signaling and apoptosis in a protein phosphatase-dependent manner[J]. Cell Death Differ,2013,20(12):1631-1643.
11. SUGIURA A,NAGASHIMA Shun,TOKUYAMA T,et al. MITOL regulates endoplasmic reticulum-mitochondria contacts via Mitofusin2[J]. Mol Cell,2013,51(1):20-34.
12. VANCE J E. Phospholipid synthesis and transport in mammalian cells[J]. Traffic,2015,16(1):1-18.
13. NAON D,SCORRANO L. At the right distance:ER-mitochondria juxtaposition in cell Life and death[J]. Biochim Biophys Acta,2014,1843(10):2184-2194.
14. LIU Z,LV Y,ZHAO N,et al. Protein kinase R-like ER kinase and its role in endoplasmic reticulum stress-decided cell fate[J]. Cell Death Dis,2015,6:e1822.
15. NGOH G A,PAPANICOLAOU K N,WALSH K. Loss of mitofusin 2 promotes endoplasmic reticulum stress[J]. J Biol Chem,2012,287(24):20321-20332.
16. MORI T,HAYASHI T,HAYASHI E,et al. Sigma-1 receptor chaperone at the ER-mitochondrion interface mediates the mitochondrion-ER-nucleus signaling for cellular survival[J]. PLoS One,2013,8(10):e76941.
17. MATSUZAKI H,FUJIMOTO T,TANAKA M,et al. Tespa1 is a novel component of mitochondria-associated endoplasmic reticulum membranes and affects mitochondrial calcium flux[J]. Biochem Biophys Res Commun,2013,433(3):322-326.
18. BRAVO R,VICENCIO J M,PARRA V,et al. Increased ER-mitochondrial coupling promotes mitochondrial respiration and bioenergetics during early phases of ER stress[J]. J Cell Sci,2011,124(Pt 13):2143-2152.
19. ARRUDA A P,PERS B M,PARLAKGVL G,et al. Chronic enrichment of hepatic endoplasmic reticulum-mitochondria contact leads to mitochondrial dysfunction in obesity[J]. Nat Med,2014,20(12):1427-1435.
20. REALI V,MEHDAWY B,NARDACCI R,et al. Reticulon protein-1C is a key component of MAMs[J]. Biochim Biophys Acta,2015,1853(3):733-745.
21. YOKOSUKA T,GOTO H,FUJII H,et al. Flow cytometric chemosensitivity assay using JC-1,a sensor of mitochondrial transmembrane potential,in acute leukemia[J]. Cancer Chemother Pharmacol,2013,72(6):1335-1342.
22. MIKHED Y,DAIBER A,STEVEN S. Mitochondrial oxidative stress,mitochondrial DNA damage and their role in age-related vascular dysfunction[J]. Int J Mol Sci,2015,16(7):15918-15953.
23. VANCE J E. MAM (mitochondria-associated membranes) in mammalian cells:lipids and beyond[J]. Biochim Biophys Acta,2014,1841(4):595-609.
24. VOLGYI K,JUHÁSZ G,KOVACS Z,et al. Dysfunction of endoplasmic reticulum (ER) and mitochondria (MT) in alzheimer's disease:the role of the ER-MT Cross-Talk[J]. Curr Alzheimer Res,2015,12(7):655-672.
25. SCHREINER B,HEDSKOG L,WIEHAGER B,et al. Amyloid-β peptides are generated in mitochondria-associated endoplasmic reticulum membranes[J]. J Alzheimers Dis,2015,43(2):369-374.
26. GUARDIA-LAGUARTA C,AREA-GOMEZ E,SCHON E A,et al. A new role for α-synuclein in Parkinson's disease:Alteration of ER-mitochondrial communication[J]. Mov Disord,2015,30(8):1026-1033.
27. CALÌ T,OTTOLINI D,NEGRO A,et al. α-Synuclein controls mitochondrial Calcium homeostasis by enhancing endoplasmic reticulum-mitochondria interactions[J]. J Biol Chem,2012,287(22):17914-17929.
28. PEINADO J R,DIAZ-RUIZ A,FR? HBECK G,et al. Mitochondria in metabolic disease:getting clues from proteomic studies[J]. Proteomics,2014,14(4/5):452-466.
29. CNOP M,FOUFELLE F,VELLOSO L A. Endoplasmic reticulum stress,obesity and diabetes[J]. Trends Mol Med,2012,18(1):59-68.
30. YUZEFOVYCH L V,MUSIYENKO S I,WILSON G L,et al. Mitochondrial DNA damage and dysfunction,and oxidative stress are associated with endoplasmic reticulum stress,protein degradation and apoptosis in high fat diet-induced insulin resistance mice[J]. PLoS One,2013,8(1):e54059.
31. SCHNEEBERGER M,DIETRICH M O,SEBASTIÁN D,et al. Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance[J]. Cell,2013,155(1):172-187.
32. GUTIÉRREZ T,PARRA V,TRONCOSO R,et al. Alteration in mitochondrial Ca(2+) uptake disrupts insulin signaling in hypertrophic cardiomyocytes[J]. Cell Commun Signal,2014,12:68.
33. BETZ C,STRACKA D,PRESCIANOTTO-BASCHONG C,et al. Feature article:mTOR complex 2-Akt signaling at mitochondria-associated endoplasmic reticulum membranes (MAM) regulates mitochondrial physiology[J]. Proc Natl Acad Sci U S A,2013,110(31):12526-12534.
34. CERQUA C,ANESTI V,PYAKUREL A,et al. Trichoplein/mitostatin regulates endoplasmic reticulum-mitochondria juxtaposition[J]. EMBO Rep,2010,11(11):854-860.
35. MARTIN L J,LAU E,SINGH H,et al. ABCC6 localizes to the mitochondria-associated membrane[J]. Circ Res,2012,111(5):516-520.
36. SUTENDRA G,DROMPARIS P,WRIGHT P,et al. The role of Nogo and the mitochondria-endoplasmic reticulum unit in pulmonary hypertension[J]. Sci Transl Med,2011,3(88):88ra55.

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