An inventory of interactors of the human HSP60/HSP10 chaperonin in the mitochondrial matrix space

Bie, Anne Sigaard; Cömert, Cagla; Körner, Roman; Corydon, Thomas J.; Palmfeldt, Johan; Hipp, Mark S.; Hartl, F. Ulrich; Bross, Peter

doi:10.1007/s12192-020-01080-6

Cited by 30 publications

(17 citation statements)

References 56 publications

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“…An integral part of this mitochondrial quality control system represents the mitochondrial chaperone heat shock protein 60 (HSP60). HSP60 interacts with its co-chaperone HSP10 and enables the proper folding of more than 300 mitochondrial matrix proteins and, thereby, mitochondrial function [ 2 , 3 ]. Important folding substrates of this complex include the antioxidative enzyme SOD2 or acyl-CoA dehydrogenases (e.g., medium-chain acyl-CoA dehydrogenase), suggesting that HSP60 influences obesity development by affecting oxidative stress and lipid utilization [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

HSP60 reduction protects against diet-induced obesity by modulating energy metabolism in adipose tissue

Hauffe

Rath

Schell

et al. 2021

Molecular Metabolism

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Objective Insulin regulates mitochondrial function, thereby propagating an efficient metabolism. Conversely, diabetes and insulin resistance are linked to mitochondrial dysfunction with a decreased expression of the mitochondrial chaperone HSP60. The aim of this investigation was to determine the effect of a reduced HSP60 expression on the development of obesity and insulin resistance. Methods Control and heterozygous whole-body HSP60 knockout (Hsp60 +/− ) mice were fed a high-fat diet (HFD, 60% calories from fat) for 16 weeks and subjected to extensive metabolic phenotyping. To understand the effect of HSP60 on white adipose tissue, microarray analysis of gonadal WAT was performed, ex vivo experiments were performed, and a lentiviral knockdown of HSP60 in 3T3-L1 cells was conducted to gain detailed insights into the effect of reduced HSP60 levels on adipocyte homeostasis. Results Male Hsp60 +/− mice exhibited lower body weight with lower fat mass. These mice exhibited improved insulin sensitivity compared to control, as assessed by Matsuda Index and HOMA-IR. Accordingly, insulin levels were significantly reduced in Hsp60 +/− mice in a glucose tolerance test. However, Hsp60 +/− mice exhibited an altered adipose tissue metabolism with elevated insulin-independent glucose uptake, adipocyte hyperplasia in the presence of mitochondrial dysfunction, altered autophagy, and local insulin resistance. Conclusions We discovered that the reduction of HSP60 in mice predominantly affects adipose tissue homeostasis, leading to beneficial alterations in body weight, body composition, and adipocyte morphology, albeit exhibiting local insulin resistance.

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Section: Introductionmentioning

confidence: 99%

HSP60 reduction protects against diet-induced obesity by modulating energy metabolism in adipose tissue

Hauffe

Rath

Schell

et al. 2021

Molecular Metabolism

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“…A released protein may rebind until it achieves a native conformation (Liu et al, 2010;Gruber and Horovitz, 2016;Hayer-Hartl et al, 2016). Chaperonins fold essential proteins in chloroplasts, mitochondria, and bacteria, as does the related group II chaperonin (CCT/TRiC) found in the eukaryotic cytosol (Kerner et al, 2005;Yam et al, 2008;Zhao and Liu, 2018;Bie et al, 2020). Though some biochemical and genetic evidence suggests E. coli GroEL (Castanié-Cornet et al, 2014) and mammalian cytosolic CCT/TRiC (Génier et al, 2016) play a role in targeting, all known functions of Cpn60 involve folding stromal proteins.…”

Section: Introductionmentioning

confidence: 99%

Chloroplast Chaperonin-Mediated Targeting of a Thylakoid Membrane Protein

2020

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“…Proteomic analysis in purified HSP60-deficient mitochondria suggested that about 20% of mitochondrial-localized proteins are HSP60-dependent, meaning they rely on HSP60 to mediate correct protein folding in the mitochondria. A survey of HSP60-interacting proteins was recently performed in HEK293 cells using coimmunoprecipitation and mass spectrometry and identified more than 300 proteins (Bie et al, 2020), 46 of which including ALDH2, CPT2, IDH3A, and SUCLG2 were downregulated in mitochondria of HSP60-deficient cardiomyocytes (Fan et al, 2019). Furthermore, an assessment of the mitochondrial protein import and stability found that deletion of HSP60 has no effect on mitochondrial protein import.…”

Section: Hsp60 Is Essential For Maintaining Mitochondrial Function and Cardiac Physiologymentioning

confidence: 99%

“…It has been shown that human HSP60 and HSP10 form a symmetrical football complex (Nisemblat et al, 2015), whereas the bacteria homolog of HSP60, GroEL, is organized in two rings, producing a barrel-like structure (Ostermann et al, 1989;Horwich et al, 2006). A survey of interactors of the human HSP60 suggested that most HSP60-interacting proteins are localized to the mitochondrial matrix space and involved in various mitochondrial functions and metabolic pathways (Bie et al, 2020). Interestingly, accumulating studies have demonstrated that HSP60 is also localized in extramitochondrial compartments including the cytosol, plasma membrane, and extracellular space, as well as in blood circulation (Meng et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Heat Shock Protein 60 in Cardiovascular Physiology and Diseases

Duan

Tang

Mitchell-Silbaugh

et al. 2020

Front. Mol. Biosci.

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Heat shock protein 60 (HSP60) is a highly conserved protein abundantly expressed in both prokaryotic and eukaryotic cells. In mammals, HSP60 has been primarily considered to reside in the mitochondria, where HSP60 and HSP10 form a complex and facilitate mitochondrial protein folding. However, HSP60 is also observed in the cytoplasm, the plasma membrane, and the extracellular space. HSP60 regulates a broad spectrum of cellular events including protein trafficking, peptide hormone signaling, cell survival, cell proliferation, inflammation, and immunization. In the cardiovascular system, growing evidence indicates that HSP60 could not only play an important role under physiological conditions, but also regulate the initiation and progression of heart failure and atherosclerosis. In this review, we focus on recent progress in understanding the function of HSP60 in cardiomyocytes, endothelial cells, and vascular smooth muscle cells (VSMCs), respectively, and discuss the related signaling pathways that have been found in these cells, so as to illustrate the role of HSP60 in the development of cardiovascular disease.

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An inventory of interactors of the human HSP60/HSP10 chaperonin in the mitochondrial matrix space

Abstract: An inventory of interactors of the human HSP60/HSP10 chaperonin in the mitochondrial matrix space. Cell stress & chaperones, 25(3), 407-416.

Cited by 30 publications

References 56 publications

HSP60 reduction protects against diet-induced obesity by modulating energy metabolism in adipose tissue

HSP60 reduction protects against diet-induced obesity by modulating energy metabolism in adipose tissue

Chloroplast Chaperonin-Mediated Targeting of a Thylakoid Membrane Protein

Heat Shock Protein 60 in Cardiovascular Physiology and Diseases

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