{"title":"Crosstalk between mitochondria-ER contact sites and the apoptotic machinery as a novel health meter.","authors":"Alvaro Larrañaga-SanMiguel, Nora Bengoa-Vergniory, Hector Flores-Romero","doi":"10.1016/j.tcb.2024.08.007","DOIUrl":null,"url":null,"abstract":"<p><p>Mitochondria-endoplasmic reticulum (ER) contact sites (MERCS) function as transient signaling platforms that regulate essential cellular functions. MERCS are enriched in specific proteins and lipids that connect mitochondria and the ER together and modulate their activities. Dysregulation of MERCS is associated with several human pathologies including Alzheimer's disease (AD), Parkinson's disease (PD), and cancer. BCL-2 family proteins can locate at MERCS and control essential cellular functions such as calcium signaling and autophagy in addition to their role in mitochondrial apoptosis. Moreover, the BCL-2-mediated apoptotic machinery was recently found to trigger cGAS-STING pathway activation and a proinflammatory response, a recognized hallmark of these diseases that requires mitochondria-ER interplay. This review underscores the pivotal role of MERCS in regulating essential cellular functions, focusing on their crosstalk with BCL-2 family proteins, and discusses how their dysregulation is linked to disease.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0000,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in Cell Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.tcb.2024.08.007","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Mitochondria-endoplasmic reticulum (ER) contact sites (MERCS) function as transient signaling platforms that regulate essential cellular functions. MERCS are enriched in specific proteins and lipids that connect mitochondria and the ER together and modulate their activities. Dysregulation of MERCS is associated with several human pathologies including Alzheimer's disease (AD), Parkinson's disease (PD), and cancer. BCL-2 family proteins can locate at MERCS and control essential cellular functions such as calcium signaling and autophagy in addition to their role in mitochondrial apoptosis. Moreover, the BCL-2-mediated apoptotic machinery was recently found to trigger cGAS-STING pathway activation and a proinflammatory response, a recognized hallmark of these diseases that requires mitochondria-ER interplay. This review underscores the pivotal role of MERCS in regulating essential cellular functions, focusing on their crosstalk with BCL-2 family proteins, and discusses how their dysregulation is linked to disease.
期刊介绍:
Trends in Cell Biology stands as a prominent review journal in molecular and cell biology. Monthly review articles track the current breadth and depth of research in cell biology, reporting on emerging developments and integrating various methods, disciplines, and principles. Beyond Reviews, the journal features Opinion articles that follow trends, offer innovative ideas, and provide insights into the implications of new developments, suggesting future directions. All articles are commissioned from leading scientists and undergo rigorous peer-review to ensure balance and accuracy.