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      Iron Supply via NCOA4-Mediated Ferritin Degradation Maintains Mitochondrial Functions

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          Abstract

          Iron is an essential nutrient for mitochondrial metabolic processes, including mitochondrial respiration. Ferritin complexes store excess iron and protect cells from iron toxicity. Therefore, iron stored in the ferritin complex might be utilized under iron-depleted conditions.

          ABSTRACT

          Iron is an essential nutrient for mitochondrial metabolic processes, including mitochondrial respiration. Ferritin complexes store excess iron and protect cells from iron toxicity. Therefore, iron stored in the ferritin complex might be utilized under iron-depleted conditions. In this study, we show that the inhibition of lysosome-dependent protein degradation by bafilomycin A1 and the knockdown of NCOA4, an autophagic receptor for ferritin, reduced mitochondrial respiration, respiratory chain complex assembly, and membrane potential under iron-sufficient conditions. However, autophagy did not contribute to degradation of the ferritin complex under iron-sufficient conditions. Knockout of the ferritin light chain, a subunit of the ferritin complex, inhibited ferritin degradation by decreasing interactions with NCOA4. However, ferritin light chain knockout did not affect mitochondrial functions under iron-sufficient conditions, and ferritin light chain knockout cells showed a rapid reduction of mitochondrial functions compared with wild-type cells under iron-depleted conditions. These results indicate that the constitutive degradation of the ferritin complex contributes to the maintenance of mitochondrial functions.

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          Author and article information

          Journal
          Mol Cell Biol
          Mol. Cell. Biol
          mcb
          mcb
          MCB
          Molecular and Cellular Biology
          American Society for Microbiology (1752 N St., N.W., Washington, DC )
          0270-7306
          1098-5549
          6 May 2019
          27 June 2019
          15 July 2019
          : 39
          : 14
          Affiliations
          [a ] Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
          [b ] Division for Development of Autophagy Modulating Drugs, Juntendo University Graduate School of Medicine, Tokyo, Japan
          [c ] Department of Applied Chemistry, National Defense Academy, Yokosuka, Kanagawa, Japan
          Author notes
          Address correspondence to Norihiko Furuya, nohuruya@ 123456juntendo.ac.jp , or Nobutaka Hattori, nhattori@ 123456juntendo.ac.jp .

          Citation Fujimaki M, Furuya N, Saiki S, Amo T, Imamichi Y, Hattori N. 2019. Iron supply via NCOA4-mediated ferritin degradation maintains mitochondrial functions. Mol Cell Biol 39:e00010-19. https://doi.org/10.1128/MCB.00010-19.

          Article
          PMC6597882 PMC6597882 6597882 00010-19
          10.1128/MCB.00010-19
          6597882
          31061094
          Copyright © 2019 American Society for Microbiology.
          Page count
          supplementary-material: 4, Figures: 5, Tables: 0, Equations: 0, References: 30, Pages: 13, Words: 6603
          Funding
          Funded by: MEXT | Japan Society for the Promotion of Science (JSPS);
          Award ID: 15K09325
          Award Recipient :
          Funded by: Ministry of Education, Culture, Sports, Science and Technology (MEXT), https://doi.org/10.13039/501100001700;
          Award ID: 25111007
          Award Recipient :
          Funded by: MEXT | Japan Society for the Promotion of Science (JSPS), https://doi.org/10.13039/501100001691;
          Award ID: 15H04842
          Award Recipient :
          Funded by: MEXT | Japan Society for the Promotion of Science (JSPS), https://doi.org/10.13039/501100001691;
          Award ID: 15H04843
          Award Recipient :
          Funded by: MEXT | Japan Society for the Promotion of Science (JSPS), https://doi.org/10.13039/501100001691;
          Award ID: 18H02744
          Award Recipient :
          Funded by: MEXT | Japan Society for the Promotion of Science (JSPS), https://doi.org/10.13039/501100001691;
          Award ID: 18KT0027
          Award Recipient :
          Funded by: MEXT | Japan Society for the Promotion of Science (JSPS), https://doi.org/10.13039/501100001691;
          Award ID: 18H04043
          Award Recipient :
          Categories
          Research Article
          Custom metadata
          July 2019

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