Abstract |
As essential regulators of mitochondrial quality control, mitochondrial dynamics and mitophagy play key roles in maintenance of metabolic health and cellular homeostasis. Here we show that knockdown of the membrane-inserted scaffolding and structural protein caveolin-1 (Cav-1) and expression of tyrosine 14 phospho-defective Cav-1 mutant (Y14F), as opposed to phospho-mimicking Y14D, altered mitochondrial morphology, and increased mitochondrial matrix mixing, mitochondrial fusion and fission dynamics as well as mitophagy in MDA-MB-231 triple negative breast cancer cells. Further, we found that interaction of Cav-1 with mitochondrial fusion/fission machinery Mitofusin 2 (Mfn2) and Dynamin related protein 1 (Drp1) was enhanced by Y14D mutant indicating Cav-1 Y14 phosphorylation prevented Mfn2 and Drp1 translocation to mitochondria. Moreover, limiting mitochondrial recruitment of Mfn2 diminished formation of the PINK1/Mfn2/Parkin complex required for initiation of mitophagy resulting in accumulation of damaged mitochondria and ROS (mtROS). Thus, these studies indicate that phospho-Cav-1 may be an important switch mechanism in cancer cell survival which could lead to novel strategies for complementing cancer therapies.
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Authors | Ying Jiang, Sarah Krantz, Xiang Qin, Shun Li, Hirushi Gunasekara, Young-Mee Kim, Adriana Zimnicka, Misuk Bae, Ke Ma, Peter T Toth, Ying Hu, Ayesha N Shajahan-Haq, Hemal H Patel, Saverio Gentile, Marcelo G Bonini, Jalees Rehman, Yiyao Liu, Richard D Minshall |
Journal | Redox biology
(Redox Biol)
Vol. 52
Pg. 102304
(06 2022)
ISSN: 2213-2317 [Electronic] Netherlands |
PMID | 35413643
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- Caveolin 1
- Mitochondrial Proteins
- Reactive Oxygen Species
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Topics |
- Caveolin 1
(genetics, metabolism)
- Mitochondria
(metabolism)
- Mitochondrial Dynamics
(physiology)
- Mitochondrial Proteins
(genetics, metabolism)
- Mitophagy
(physiology)
- Reactive Oxygen Species
(metabolism)
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