Presenilin-2 Modulation of ER-mitochondria Interactions: FAD Mutations, Mechanisms and Pathological Consequences

Overview

Journal Commun Integr Biol

Specialty Biology

Date 2011 Oct 8

PMID 21980580

Citations 16

Authors

Enrico Zampese

Cristina Fasolato

Tullio Pozzan

Paola Pizzo

Affiliations

Soon will be listed here.

Abstract

Presenilin (PS) mutations are the main cause of Familial Alzheimer's Disease (FAD) and have been demonstrated to cause an imbalance of intracellular Ca(2+) homeostasis. Though PS1 and 2 are generally considered to behave similarly in terms of their effects on Ca(2+) handling, we have recently described a novel function, which is unique to PS2, i.e., the modulation of ER-mitochondria juxtaposition. Accordingly, PS2, but not PS1, affects the Ca(2+) cross-talk between these organelles, a key feature in determining cell fate. In particular, PS2 overexpression, and more drastically that of FAD-linked PS2 mutants, strongly increases the interaction between ER and mitochondria, thus facilitating mitochondrial Ca(2+) uptake. The likely mechanisms behind this phenomenon and its potential effects in cell physiology and pathology are discussed.

Citing Articles

Mitochondrial Alterations in Alzheimer's Disease: Insight from the 5xFAD Mouse Model.

Keskinoz E, Celik M, Toklucu E, Birisik K, Erisir A, Oz-Arslan D Mol Neurobiol. 2024; .

PMID: 39658775 DOI: 10.1007/s12035-024-04632-4.

Presenilins and mitochondria-an intriguing link: mini-review.

Makarov M, Kushnireva L, Papa M, Korkotian E Front Neurosci. 2023; 17:1249815.

PMID: 37575294 PMC: 10416233. DOI: 10.3389/fnins.2023.1249815.

Transmembrane BAX inhibitor motif containing 6 suppresses presenilin-2 to preserve mitochondrial integrity after myocardial ischemia-reperfusion injury.

Ma L, Liao L, Zhou N, Tao H, Zhou H, Tan Y Int J Biol Sci. 2023; 19(4):1228-1240.

PMID: 36923943 PMC: 10008687. DOI: 10.7150/ijbs.81100.

Mitochondrial Calcium: Effects of Its Imbalance in Disease.

Matuz-Mares D, Gonzalez-Andrade M, Araiza-Villanueva M, Vilchis-Landeros M, Vazquez-Meza H Antioxidants (Basel). 2022; 11(5).

PMID: 35624667 PMC: 9138001. DOI: 10.3390/antiox11050801.

Potential mechanisms underlying lithium treatment for Alzheimer's disease and COVID-19.

Wei H, Anchipolovsky S, Vera R, Liang G, Chuang D Eur Rev Med Pharmacol Sci. 2022; 26(6):2201-2214.

PMID: 35363371 PMC: 9173589. DOI: 10.26355/eurrev_202203_28369.

References

Bojarski L, Herms J, Kuznicki J . Calcium dysregulation in Alzheimer's disease. Neurochem Int. 2007; 52(4-5):621-33. DOI: 10.1016/j.neuint.2007.10.002. View

Pinton P, Giorgi C, Siviero R, Zecchini E, Rizzuto R . Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis. Oncogene. 2008; 27(50):6407-18. PMC: 2844952. DOI: 10.1038/onc.2008.308. View

Csordas G, Varnai P, Golenar T, Roy S, Purkins G, Schneider T . Imaging interorganelle contacts and local calcium dynamics at the ER-mitochondrial interface. Mol Cell. 2010; 39(1):121-32. PMC: 3178184. DOI: 10.1016/j.molcel.2010.06.029. View

Rizzuto R, Pinton P, Carrington W, Fay F, Fogarty K, Lifshitz L . Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science. 1998; 280(5370):1763-6. DOI: 10.1126/science.280.5370.1763. View

De Strooper B, Annaert W . Novel research horizons for presenilins and γ-secretases in cell biology and disease. Annu Rev Cell Dev Biol. 2010; 26:235-60. DOI: 10.1146/annurev-cellbio-100109-104117. View

Zhang C, Wu B, Beglopoulos V, Wines-Samuelson M, Zhang D, Dragatsis I . Presenilins are essential for regulating neurotransmitter release. Nature. 2009; 460(7255):632-6. PMC: 2744588. DOI: 10.1038/nature08177. View

Szabadkai G, Bianchi K, Varnai P, De Stefani D, Wieckowski M, Cavagna D . Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels. J Cell Biol. 2006; 175(6):901-11. PMC: 2064700. DOI: 10.1083/jcb.200608073. View

Zampese E, Fasolato C, Kipanyula M, Bortolozzi M, Pozzan T, Pizzo P . Presenilin 2 modulates endoplasmic reticulum (ER)-mitochondria interactions and Ca2+ cross-talk. Proc Natl Acad Sci U S A. 2011; 108(7):2777-82. PMC: 3041131. DOI: 10.1073/pnas.1100735108. View

Zatti G, Burgo A, Giacomello M, Barbiero L, Ghidoni R, Sinigaglia G . Presenilin mutations linked to familial Alzheimer's disease reduce endoplasmic reticulum and Golgi apparatus calcium levels. Cell Calcium. 2006; 39(6):539-50. DOI: 10.1016/j.ceca.2006.03.002. View

10.

Contreras L, Drago I, Zampese E, Pozzan T . Mitochondria: the calcium connection. Biochim Biophys Acta. 2010; 1797(6-7):607-18. DOI: 10.1016/j.bbabio.2010.05.005. View

11.

Bai G, Chivatakarn O, Bonanomi D, Lettieri K, Franco L, Xia C . Presenilin-dependent receptor processing is required for axon guidance. Cell. 2011; 144(1):106-18. PMC: 3034090. DOI: 10.1016/j.cell.2010.11.053. View

12.

Pizzo P, Pozzan T . Mitochondria-endoplasmic reticulum choreography: structure and signaling dynamics. Trends Cell Biol. 2007; 17(10):511-7. DOI: 10.1016/j.tcb.2007.07.011. View

13.

Martins de Brito O, Scorrano L . Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature. 2008; 456(7222):605-10. DOI: 10.1038/nature07534. View

14.

Liu X, Hajnoczky G . Ca2+-dependent regulation of mitochondrial dynamics by the Miro-Milton complex. Int J Biochem Cell Biol. 2009; 41(10):1972-6. PMC: 2742205. DOI: 10.1016/j.biocel.2009.05.013. View

15.

Parks A, Curtis D . Presenilin diversifies its portfolio. Trends Genet. 2007; 23(3):140-50. DOI: 10.1016/j.tig.2007.01.008. View

16.

Vetrivel K, Zhang Y, Xu H, Thinakaran G . Pathological and physiological functions of presenilins. Mol Neurodegener. 2006; 1:4. PMC: 1513131. DOI: 10.1186/1750-1326-1-4. View

17.

Hayashi T, Rizzuto R, Hajnoczky G, Su T . MAM: more than just a housekeeper. Trends Cell Biol. 2009; 19(2):81-8. PMC: 2750097. DOI: 10.1016/j.tcb.2008.12.002. View

18.

Iwasawa R, Mahul-Mellier A, Datler C, Pazarentzos E, Grimm S . Fis1 and Bap31 bridge the mitochondria-ER interface to establish a platform for apoptosis induction. EMBO J. 2010; 30(3):556-68. PMC: 3034017. DOI: 10.1038/emboj.2010.346. View

19.

Lai M, Chen E, Crouthamel M, DiMuzio-Mower J, Xu M, Huang Q . Presenilin-1 and presenilin-2 exhibit distinct yet overlapping gamma-secretase activities. J Biol Chem. 2003; 278(25):22475-81. DOI: 10.1074/jbc.M300974200. View

20.

Shen J, Kelleher 3rd R . The presenilin hypothesis of Alzheimer's disease: evidence for a loss-of-function pathogenic mechanism. Proc Natl Acad Sci U S A. 2007; 104(2):403-9. PMC: 1766397. DOI: 10.1073/pnas.0608332104. View