Spermidine activates mitochondrial trifunctional protein and improves antitumor immunity in mice-Reference-Cited by-同舟云学术

Spermidine activates mitochondrial trifunctional protein and improves antitumor immunity in mice

Published:2022-10-28 Issue:6618 Volume:378 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Al-Habsi Muna¹²³^ORCID,Chamoto Kenji¹^ORCID,Matsumoto Ken⁴^ORCID,Nomura Norimichi⁵^ORCID,Zhang Baihao⁶^ORCID,Sugiura Yuki⁷^ORCID,Sonomura Kazuhiro⁸⁹,Maharani Aprilia¹^ORCID,Nakajima Yuka¹^ORCID,Wu Yibo¹⁰¹¹^ORCID,Nomura Yayoi⁵,Menzies Rosemary¹^ORCID,Tajima Masaki³^ORCID,Kitaoka Koji¹^ORCID,Haku Yasuharu¹^ORCID,Delghandi Sara¹^ORCID,Yurimoto Keiko¹^ORCID,Matsuda Fumihiko⁸^ORCID,Iwata So⁵^ORCID,Ogura Toshihiko⁴^ORCID,Fagarasan Sidonia³⁶^ORCID,Honjo Tasuku¹^ORCID

Affiliation:

1. Division of Immunology and Genomic Medicine, Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

2. National Genetic Center, Ministry of Health, Muscat, Oman.

3. Division of Integrated High-Order Regulatory Systems, Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

4. Department of Developmental Neurobiology, Institute of Development, Aging and Cancer, Tohoku University, Miyagi, Japan.

5. Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

6. Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Yokohama, Japan.

7. Department of Biochemistry, Keio University, Tokyo, Japan.

8. Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

9. Life Science Research Center, Technology Research Laboratory, Shimadzu Corporation, Kyoto, Japan.

10. YCI Laboratory for Next-Generation Proteomics, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Yokohama, Japan.

11. Chemical Biology Mass Spectrometry Platform, Faculty of Science, University of Geneva, Geneva, Switzerland.

Abstract

Spermidine (SPD) delays age-related pathologies in various organisms. SPD supplementation overcame the impaired immunotherapy against tumors in aged mice by increasing mitochondrial function and activating CD8 + T cells. Treatment of naïve CD8 + T cells with SPD acutely enhanced fatty acid oxidation. SPD conjugated to beads bound to the mitochondrial trifunctional protein (MTP). In the MTP complex, synthesized and purified from Escherichia coli , SPD bound to the α and β subunits of MTP with strong affinity and allosterically enhanced their enzymatic activities. T cell–specific deletion of the MTP α subunit abolished enhancement of programmed cell death protein 1 (PD-1) blockade immunotherapy by SPD, indicating that MTP is required for SPD-dependent T cell activation.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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