A VDAC1-mediated NEET protein chain transfers [2Fe-2S] clusters between the mitochondria and the cytosol and impacts mitochondrial dynamics

Author:

Karmi Ola123,Marjault Henri-Baptiste12,Bai Fang45678ORCID,Roy Susmita9ORCID,Sohn Yang-Sung12,Darash Yahana Merav12,Morcos Faruck1011ORCID,Ioannidis Konstantinos1212,Nahmias Yaakov1212,Jennings Patricia A.13,Mittler Ron3ORCID,Onuchic José N.456ORCID,Nechushtai Rachel12

Affiliation:

1. The Alexander Silberman Institute of Life Science, Faculty of Science and Mathematics, The Hebrew University of Jerusalem, Jerusalem 91904, Israel

2. The Wolfson Centre for Applied Structural Biology, Faculty of Science and Mathematics, The Hebrew University of Jerusalem, Jerusalem 91904, Israel

3. Department of Surgery, University of Missouri School of Medicine, University of Missouri, Columbia, MO 65211

4. Center for Theoretical Biological Physics, Department of Physics and Astronomy, Rice University, Houston, TX 77005

5. Department of Chemistry, Rice University, Houston, TX 77005

6. Department of Biosciences, Rice University, Houston, TX 77005

7. Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210 China

8. School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China

9. Indian Institute of Science Education and Research Kolkata, West Bengal 741246, India

10. Department of Biological Sciences, University of Texas at Dallas, Richardson, TX 75080

11. Department of Bioengineering, University of Texas at Dallas, Richardson, TX 75080

12. Alexander Grass Center for Bioengineering, The Hebrew University of Jerusalem, Jerusalem 91904, Israel

13. Department of Chemistry & Biochemistry, University of California San Diego, La Jolla, CA 92093

Abstract

Significance Here we address the important question of cross-talk between the mitochondria and cytosol. We show that the inner mitochondrial protein, MiNT, interacts with a protein on the outer mitochondrial membrane (mNT). This interaction occurs within the major outer membrane protein VDAC1. Inside the inner space of VDAC1, MiNT transfers its [2Fe-2S] clusters to mNT, which was shown to be a [2Fe-2S] cluster donor protein that donates its cluster(s) to apo-acceptor proteins residing in the cytosol. Hence, we suggest a pathway for transferring [2Fe-2S] clusters from inside the mitochondria to the cytosol.

Funder

National Science Foundation

Welch Foundation

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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