Chaperone mediated autophagy contributes to the newly synthesized histones H3 and H4 quality control

Juan Hormazabal; Francisco Saavedra; Claudia Espinoza-Arratia; Nicolas W. Martinez; Tatiana Cruces; Iván E. Alfaro; Alejandra Loyola

doi:10.1093/nar/gkab1296

Chaperone mediated autophagy contributes to the newly synthesized histones H3 and H4 quality control

Juan Hormazabal, Francisco Saavedra, Claudia Espinoza-Arratia, Nicolas W. Martinez, Tatiana Cruces, Iván E. Alfaro^*, Alejandra Loyola^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Although there are several pathways to ensure that proteins are folded properly in the cell, little is known about the molecular mechanisms regulating histone folding and proteostasis. In this work, we identified that chaperone-mediated autophagy (CMA) is the main pathway involved in the degradation of newly synthesized histones H3 and H4. This degradation is finely regulated by the interplay between HSC70 and tNASP, two histone interacting proteins. tNASP stabilizes histone H3 levels by blocking the direct transport of histone H3 into lysosomes. We further demonstrate that CMA degrades unfolded histone H3. Thus, we reveal that CMA is the main degradation pathway involved in the quality control of histone biogenesis, evidencing an additional mechanism in the intricate network of histone cellular proteostasis.

Original language	English
Pages (from-to)	1875-1887
Number of pages	13
Journal	Nucleic Acids Research
Volume	50
Issue number	4
DOIs	https://doi.org/10.1093/nar/gkab1296
State	Published - 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.

ASJC Scopus subject areas

Genetics

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10.1093/nar/gkab1296

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title = "Chaperone mediated autophagy contributes to the newly synthesized histones H3 and H4 quality control",

abstract = "Although there are several pathways to ensure that proteins are folded properly in the cell, little is known about the molecular mechanisms regulating histone folding and proteostasis. In this work, we identified that chaperone-mediated autophagy (CMA) is the main pathway involved in the degradation of newly synthesized histones H3 and H4. This degradation is finely regulated by the interplay between HSC70 and tNASP, two histone interacting proteins. tNASP stabilizes histone H3 levels by blocking the direct transport of histone H3 into lysosomes. We further demonstrate that CMA degrades unfolded histone H3. Thus, we reveal that CMA is the main degradation pathway involved in the quality control of histone biogenesis, evidencing an additional mechanism in the intricate network of histone cellular proteostasis.",

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AU - Hormazabal, Juan

AU - Saavedra, Francisco

AU - Espinoza-Arratia, Claudia

AU - Martinez, Nicolas W.

AU - Cruces, Tatiana

AU - Alfaro, Iván E.

AU - Loyola, Alejandra

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AB - Although there are several pathways to ensure that proteins are folded properly in the cell, little is known about the molecular mechanisms regulating histone folding and proteostasis. In this work, we identified that chaperone-mediated autophagy (CMA) is the main pathway involved in the degradation of newly synthesized histones H3 and H4. This degradation is finely regulated by the interplay between HSC70 and tNASP, two histone interacting proteins. tNASP stabilizes histone H3 levels by blocking the direct transport of histone H3 into lysosomes. We further demonstrate that CMA degrades unfolded histone H3. Thus, we reveal that CMA is the main degradation pathway involved in the quality control of histone biogenesis, evidencing an additional mechanism in the intricate network of histone cellular proteostasis.

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Chaperone mediated autophagy contributes to the newly synthesized histones H3 and H4 quality control

Abstract

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