Elucidation of the interaction proteome of mitochondrial chaperone Hsp78 highlights its role in protein aggregation during heat stress

Jaworek, Witold; Sylvester, Marc; Cenini, Giovanna; Voos, Wolfgang

doi:10.1016/j.jbc.2022.102494

Cited by 5 publications

(5 citation statements)

References 46 publications

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“…Previous studies have characterized both the interactome of Hsp78 and the composition of aggregates isolated from yeast cells after a heat shock 27,28 . To identify common hits and thereby get an understanding of the general propensities of aggregating proteins, we reanalyzed these datasets.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have characterized both the interactome of Hsp78 and the composition of aggregates isolated from yeast cells after a heat shock. 27 , 28 To identify common hits and thereby get an understanding of the general propensities of aggregating proteins, we reanalyzed these datasets. This analysis revealed a common set of very abundant, soluble matrix proteins 6 that are part of the aggregates and interact with Hsp78 upon heat stress (Figure 3A ).…”

Section: Resultsmentioning

confidence: 99%

“…(A) Bioinformatic analysis of aggregation prone proteins that interact with Hsp78 under heat shock at 42°C (green). Data extracted from Jaworek et al 27 Connecting lines are quantitatively color‐coded according to the fold change (Fc). (B) Representation of Hsp78 significant negative genetic interactors (cutoff score < −0.12, p < 0.05).…”

Section: Resultsmentioning

confidence: 99%

“…Deposited data from Jaworek et al 27 were reanalyzed. To that end, the abundance of proteins (present in at least two of three biological replicates) identified in mitochondrial aggregates during heat stress (42°C) were compared with control conditions (25°C).…”

Section: Methodsmentioning

confidence: 99%

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Newly imported proteins in mitochondria are particularly sensitive to aggregation

et al. 2023

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Aim A functional proteome is essential for life and maintained by protein quality control (PQC) systems in the cytosol and organelles. Protein aggregation is an indicator of a decline of PQC linked to aging and disease. Mitochondrial PQC is critical to maintain mitochondrial function and thus cellular fitness. How mitochondria handle aggregated proteins is not well understood. Here we tested how the metabolic status impacts on formation and clearance of aggregates within yeast mitochondria and assessed which proteins are particularly sensitive to denaturation. Methods Confocal microscopy, electron microscopy, immunoblotting and genetics were applied to assess mitochondrial aggregate handling in response to heat shock and ethanol using the mitochondrial disaggregase Hsp78 as a marker for protein aggregates. Results We show that aggregates formed upon heat or ethanol stress with different dynamics depending on the metabolic state. While fermenting cells displayed numerous small aggregates that coalesced into one large foci that was resistant to clearance, respiring cells showed less aggregates and cleared these aggregates more efficiently. Acute inhibition of mitochondrial translation had no effect, while preventing protein import into mitochondria by inhibition of cytosolic translation prevented aggregate formation. Conclusion Collectively, our data show that the metabolic state of the cells impacts the dynamics of aggregate formation and clearance, and that mainly newly imported and not yet assembled proteins are prone to form aggregates. Because mitochondrial functionality is crucial for cellular metabolism, these results highlight the importance of efficient protein biogenesis to maintain the mitochondrial proteome operational during metabolic adaptations and cellular stress.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Newly imported proteins in mitochondria are particularly sensitive to aggregation

et al. 2023

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“…The heating of cells leads to an increased expression of heat-shock proteins (HSPs) in mitochondria [150][151][152]. Theoretically, high levels of HSPs in mitochondria can be an indicator of elevated mitochondrial temperature.…”

Section: Avoidance Of Thermal Damagementioning

confidence: 99%

Warm Cells, Hot Mitochondria: Achievements and Problems of Ultralocal Thermometry

Kruglov,

Romshin,

Nikiforova

et al. 2023

IJMS

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Temperature is a crucial regulator of the rate and direction of biochemical reactions and cell processes. The recent data indicating the presence of local thermal gradients associated with the sites of high-rate thermogenesis, on the one hand, demonstrate the possibility for the existence of “thermal signaling” in a cell and, on the other, are criticized on the basis of thermodynamic calculations and models. Here, we review the main thermometric techniques and sensors developed for the determination of temperature inside living cells and diverse intracellular compartments. A comparative analysis is conducted of the results obtained using these methods for the cytosol, nucleus, endo-/sarcoplasmic reticulum, and mitochondria, as well as their biological consistency. Special attention is given to the limitations, possible sources of errors and ambiguities of the sensor’s responses. The issue of biological temperature limits in cells and organelles is considered. It is concluded that the elaboration of experimental protocols for ultralocal temperature measurements that take into account both the characteristics of biological systems, as well as the properties and limitations of each type of sensor is of critical importance for the generation of reliable results and further progress in this field.

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Master players in the chase of establishing heat tolerance: a molecular perspective

Chaudhary,

Badoni,

Chauhan

2024

Current Omics Advancement in Plant Abiotic Stress Biology

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Elucidation of the interaction proteome of mitochondrial chaperone Hsp78 highlights its role in protein aggregation during heat stress

Cited by 5 publications

References 46 publications

Newly imported proteins in mitochondria are particularly sensitive to aggregation

Newly imported proteins in mitochondria are particularly sensitive to aggregation

Warm Cells, Hot Mitochondria: Achievements and Problems of Ultralocal Thermometry

Master players in the chase of establishing heat tolerance: a molecular perspective

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