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AbuEid M, McAllister DM, McOlash L, et al. Synchronous effects of targeted mitochondrial complex I inhibitors on tumor and immune cells abrogate melanoma progression. iScience. 2021;24(6):102653doi: 10.1016/j.isci.2021.102653.
AbuEid, M., McAllister, D. M., McOlash, L., Harwig, M. C., Cheng, G., Drouillard, D., Boyle, K. A., Hardy, M., Zielonka, J., Johnson, B. D., Hill, R. B., Kalyanaraman, B., & Dwinell, M. B. (2021). Synchronous effects of targeted mitochondrial complex I inhibitors on tumor and immune cells abrogate melanoma progression. iScience, 24(6), 102653. https://doi.org/10.1016/j.isci.2021.102653
AbuEid, Mahmoud, et al. "Synchronous effects of targeted mitochondrial complex I inhibitors on tumor and immune cells abrogate melanoma progression." iScience vol. 24,6 (2021): 102653. doi: https://doi.org/10.1016/j.isci.2021.102653
AbuEid M, McAllister DM, McOlash L, Harwig MC, Cheng G, Drouillard D, Boyle KA, Hardy M, Zielonka J, Johnson BD, Hill RB, Kalyanaraman B, Dwinell MB. Synchronous effects of targeted mitochondrial complex I inhibitors on tumor and immune cells abrogate melanoma progression. iScience. 2021 May 25;24(6):102653. doi: 10.1016/j.isci.2021.102653. eCollection 2021 Jun 25. PMID: 34189432; PMCID: PMC8220235.
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iScience. 2021 May 25;24(6):102653. doi: 10.1016/j.isci.2021.102653. eCollection 2021 Jun 25.

Synchronous effects of targeted mitochondrial complex I inhibitors on tumor and immune cells abrogate melanoma progression.

iScience

Mahmoud AbuEid, Donna M McAllister, Laura McOlash, Megan Cleland Harwig, Gang Cheng, Donovan Drouillard, Kathleen A Boyle, Micael Hardy, Jacek Zielonka, Bryon D Johnson, R Blake Hill, Balaraman Kalyanaraman, Michael B Dwinell

Affiliations

  1. Department of Microbiology & Immunology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
  2. Center for Immunology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
  3. Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
  4. Department of Biophysics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
  5. Aix Marseille University, CNRS, ICR, UMR 7273, Marseille 13013, France.
  6. Cancer Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
  7. Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.

PMID: 34189432 PMCID: PMC8220235 DOI: 10.1016/j.isci.2021.102653

Abstract

Metabolic heterogeneity within the tumor microenvironment promotes cancer cell growth and immune suppression. We determined the impact of mitochondria-targeted complex I inhibitors (Mito-CI) in melanoma. Mito-CI decreased mitochondria complex I oxygen consumption, Akt-FOXO signaling, blocked cell cycle progression, melanoma cell proliferation and tumor progression in an immune competent model system. Immune depletion revealed roles for T cells in the antitumor effects of Mito-CI. While Mito-CI preferentially accumulated within and halted tumor cell proliferation, it also elevated infiltration of activated effector T cells and decreased myeloid-derived suppressor cells (MDSC) as well as tumor-associated macrophages (TAM) in melanoma tumors

© 2021 The Authors.

Keywords: Cancer; Cell biology; Components of the immune system

Conflict of interest statement

MBD is a co-founder and has ownership and financial interests in Protein Foundry, LLC and Xlock Biosciences, LLC. BK has a composition of matter and application of use patent on the manufacture and us

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