High-mobility Group Box 1 is Essential for Mitochondrial Quality Control

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2011 Jun 7

PMID 21641551

Citations 160

Authors

Daolin Tang

Rui Kang

Kristen M Livesey

Guido Kroemer

Timothy R Billiar

Bennett Van Houten

Herbert J Zeh 3rd

Michael T Lotze

Affiliations

Soon will be listed here.

Abstract

Mitochondria are organelles centrally important for bioenergetics as well as regulation of apoptotic death in eukaryotic cells. High-mobility group box 1 (HMGB1), an evolutionarily conserved chromatin-associated protein which maintains nuclear homeostasis, is also a critical regulator of mitochondrial function and morphology. We show that heat shock protein beta-1 (HSPB1 or HSP27) is the downstream mediator of this effect. Disruption of the HSPB1 gene in embryonic fibroblasts with wild-type HMGB1 recapitulates the mitochondrial fragmentation, deficits in mitochondrial respiration, and adenosine triphosphate (ATP) synthesis observed with targeted deletion of HMGB1. Forced expression of HSPB1 reverses this phenotype in HMGB1 knockout cells. Mitochondrial effects mediated by HMGB1 regulation of HSPB1 expression serve as a defense against mitochondrial abnormality, enabling clearance and autophagy in the setting of cellular stress. Our findings reveal an essential role for HMGB1 in autophagic surveillance with important effects on mitochondrial quality control.

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