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Miro proteins and their role in mitochondrial transfer in cancer and beyond
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SYSNO ASEP 0565970 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Miro proteins and their role in mitochondrial transfer in cancer and beyond Author(s) Nahácka, Zuzana (BTO-N)
Novák, Jaromír (BTO-N)
Zobalová, Renata (BTO-N) RID
Neužil, Jiří (BTO-N) RIDNumber of authors 4 Article number 937753 Source Title Frontiers in Cell and Developmental Biology. - : Frontiers Research Foundation - ISSN 2296-634X
Roč. 10, JUL 25 2022 (2022)Number of pages 18 s. Language eng - English Country CH - Switzerland Keywords cancer ; mitochondria ; intercellular transfer ; Miro ; respiration ; migration ; metastasis Subject RIV EB - Genetics ; Molecular Biology OECD category Developmental biology R&D Projects GX21-04607X GA ČR - Czech Science Foundation (CSF) LM2018129 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GA20-05942S GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support BTO-N - RVO:86652036 UT WOS 000891264200001 EID SCOPUS 85135527380 DOI 10.3389/fcell.2022.937753 Annotation Mitochondria are organelles essential for tumor cell proliferation and metastasis. Although their main cellular function, generation of energy in the form of ATP is dispensable for cancer cells, their capability to drive their adaptation to stress originating from tumor microenvironment makes them a plausible therapeutic target. Recent research has revealed that cancer cells with damaged oxidative phosphorylation import healthy (functional) mitochondria from surrounding stromal cells to drive pyrimidine synthesis and cell proliferation. Furthermore, it has been shown that energetically competent mitochondria are fundamental for tumor cell migration, invasion and metastasis. The spatial positioning and transport of mitochondria involves Miro proteins from a subfamily of small GTPases, localized in outer mitochondrial membrane. Miro proteins are involved in the structure of the MICOS complex, connecting outer and inner-mitochondrial membrane, in mitochondria-ER communication, Ca2+ metabolism,and in the recycling of damaged organelles via mitophagy. The most important role of Miro is regulation of mitochondrial movement and distribution within (and between) cells, acting as an adaptor linking organelles to cytoskeleton-associated motor proteins. In this review, we discuss the function of Miro proteins in various modes of intercellular mitochondrial transfer, emphasizing the structure and dynamics of tunneling nanotubes, the most common transfer modality. We summarize the evidence for and propose possible roles of Miro proteins in nanotube-mediated transfer as well as in cancer cell migration and metastasis, both processes being tightly connected to cytoskeleton-driven mitochondrial movement and positioning. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2023 Electronic address https://www.frontiersin.org/articles/10.3389/fcell.2022.937753/full
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