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LONP1 and mtHSP70 cooperate to promote mitochondrial protein folding

Author

Listed:
  • Chun-Shik Shin

    (California Institute of Technology)

  • Shuxia Meng

    (California Institute of Technology)

  • Spiros D. Garbis

    (California Institute of Technology)

  • Annie Moradian

    (California Institute of Technology
    Cedars-Sinai Medical Center)

  • Robert W. Taylor

    (Newcastle University)

  • Michael J. Sweredoski

    (California Institute of Technology
    Kaiser Permanente)

  • Brett Lomenick

    (California Institute of Technology)

  • David C. Chan

    (California Institute of Technology)

Abstract

Most mitochondrial precursor polypeptides are imported from the cytosol into the mitochondrion, where they must efficiently undergo folding. Mitochondrial precursors are imported as unfolded polypeptides. For proteins of the mitochondrial matrix and inner membrane, two separate chaperone systems, HSP60 and mitochondrial HSP70 (mtHSP70), facilitate protein folding. We show that LONP1, an AAA+ protease of the mitochondrial matrix, works with the mtHSP70 chaperone system to promote mitochondrial protein folding. Inhibition of LONP1 results in aggregation of a protein subset similar to that caused by knockdown of DNAJA3, a co-chaperone of mtHSP70. LONP1 is required for DNAJA3 and mtHSP70 solubility, and its ATPase, but not its protease activity, is required for this function. In vitro, LONP1 shows an intrinsic chaperone-like activity and collaborates with mtHSP70 to stabilize a folding intermediate of OXA1L. Our results identify LONP1 as a critical factor in the mtHSP70 folding pathway and demonstrate its proposed chaperone activity.

Suggested Citation

  • Chun-Shik Shin & Shuxia Meng & Spiros D. Garbis & Annie Moradian & Robert W. Taylor & Michael J. Sweredoski & Brett Lomenick & David C. Chan, 2021. "LONP1 and mtHSP70 cooperate to promote mitochondrial protein folding," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20597-z
    DOI: 10.1038/s41467-020-20597-z
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    Cited by:

    1. Jonas Benjamin Michaelis & Melinda Elaine Brunstein & Süleyman Bozkurt & Ludovico Alves & Martin Wegner & Manuel Kaulich & Christian Pohl & Christian Münch, 2022. "Protein import motor complex reacts to mitochondrial misfolding by reducing protein import and activating mitophagy," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Pascale Baden & Maria Jose Perez & Hariam Raji & Federico Bertoli & Stefanie Kalb & María Illescas & Fokion Spanos & Claudio Giuliano & Alessandra Maria Calogero & Marvin Oldrati & Hannah Hebestreit &, 2023. "Glucocerebrosidase is imported into mitochondria and preserves complex I integrity and energy metabolism," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    3. Geut Galai & Xie He & Barak Rotblat & Shai Pilosof, 2023. "Ecological network analysis reveals cancer-dependent chaperone-client interaction structure and robustness," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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