線粒體相關內質網膜
線粒體相關內質網膜（英語：Mitochondria-Associated Endoplasmic Reticulum Membrane, MAM）是內質網與線粒體之間的物理接觸結構，不僅參與細胞內多條生物通路，還在脂質代謝、鈣穩態、線粒體動力學、自噬、炎症反應和內質網應激等方面發揮重要功能[1]。整個MAM蛋白質組可能包括900~1200個蛋白質[2][3]。
發現與分類
MAM首次發現於1950年代，當時科學家們通過電子顯微鏡觀察到了內質網與線粒體之間的相互連接[4]。到1990年代，科學家通過生化手段分離出與線粒體外膜緊密接觸的內質網亞結構，正式定義了MAM[1]。
根據結構特徵，MAM可分為三類[5]：
- 覆蓋約50%線粒體表面的內質網突起；
- 包裹整個線粒體的內質網小管；
- 覆蓋約10%線粒體表面的單一接觸點。
功能
MAM是鈣信號傳遞的重要平台，負責從內質網向線粒體傳遞鈣離子信號，線粒體隨後解碼這些信號，調節諸如能量代謝、細胞凋亡等基本功能[1]。
MAM是脂質合成與代謝的關鍵區域，許多脂質合成相關蛋白定位於此。包括膽固醇酰基轉移酶1（ACAT1/SOAT1）[6]、二酰基甘油酰基轉移酶2（DGAT2）[7]、磷脂酰絲氨酸合酶等[8]，這些蛋白負責膽固醇酯的形成、脂肪代謝以及磷脂合成[1]。
在MAM區域，許多內質網和線粒體蛋白相互作用，形成了複雜的複合體[1]。例如，位於內質網的絲裂原蛋白2（MFN2）與線粒體的MFN1和MFN2形成異型和同型接觸[9]；內質網的B細胞受體相關蛋白31（BAP31）與線粒體裂變蛋白1（FIS1）相互作用[10]。
參考文獻
- ^ 1.0 1.1 1.2 1.3 1.4 Qu, ChuanRen; Liu, Lei. Endoplasmic reticulum-mitochondrial interaction and calcium homeostasis. SCIENTIA SINICA Vitae. 2024-07-01. doi:10.1360/SSV-2024-0103.
- ^ Poston, Chloe N.; Krishnan, Srinivasan C.; Bazemore-Walker, Carthene R. In-depth proteomic analysis of mammalian mitochondria-associated membranes (MAM). Journal of Proteomics. 2013-02, 79: 219–230. doi:10.1016/j.jprot.2012.12.018.
- ^ Zhang, Aiping; Williamson, Chad D.; Wong, Daniel S.; Bullough, Matthew D.; Brown, Kristy J.; Hathout, Yetrib; Colberg-Poley, Anamaris M. Quantitative Proteomic Analyses of Human Cytomegalovirus-Induced Restructuring of Endoplasmic Reticulum-Mitochondrial Contacts at Late Times of Infection. Molecular & Cellular Proteomics. 2011-10, 10 (10): M111.009936. doi:10.1074/mcp.M111.009936.
- ^ Bernhard, W.; Rouiller, C. CLOSE TOPOGRAPHICAL RELATIONSHIP BETWEEN MITOCHONDRIA AND ERGASTOPLASM OF LIVER CELLS IN A DEFINITE PHASE OF CELLULAR ACTIVITY. The Journal of Cell Biology. 1956-07-25, 2 (4): 73–78. doi:10.1083/jcb.2.4.73.
- ^ Fujimoto, M; Hayashi, T. New insights into the role of mitochondria-associated endoplasmic reticulum membrane.. International review of cell and molecular biology. 2011, 292: 73–117. PMID 22078959. doi:10.1016/B978-0-12-386033-0.00002-5.
- ^ Vance, Jean E. MAM (mitochondria-associated membranes) in mammalian cells: Lipids and beyond. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2014-04, 1841 (4): 595–609. doi:10.1016/j.bbalip.2013.11.014.
- ^ Stone, Scot J.; Levin, Malin C.; Zhou, Ping; Han, Jiayi; Walther, Tobias C.; Farese, Robert V. The Endoplasmic Reticulum Enzyme DGAT2 Is Found in Mitochondria-associated Membranes and Has a Mitochondrial Targeting Signal That Promotes Its Association with Mitochondria. Journal of Biological Chemistry. 2009-02, 284 (8): 5352–5361. doi:10.1074/jbc.M805768200.
- ^ Stone, Scot J.; Vance, Jean E. Phosphatidylserine Synthase-1 and -2 Are Localized to Mitochondria-associated Membranes. Journal of Biological Chemistry. 2000-11, 275 (44): 34534–34540. doi:10.1074/jbc.M002865200.
- ^ de Brito, Olga Martins; Scorrano, Luca. Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature. 2008-12-04, 456 (7222): 605–610. doi:10.1038/nature07534.
- ^ Iwasawa, Ryota; Mahul-Mellier, Anne-Laure; Datler, Christoph; Pazarentzos, Evangelos; Grimm, Stefan. Fis1 and Bap31 bridge the mitochondria-ER interface to establish a platform for apoptosis induction: Fis1 induces apoptosis via Bap31. The EMBO Journal. 2011-02-02, 30 (3): 556–568. doi:10.1038/emboj.2010.346.