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Shotgun measurements of proteome fractionations: mitochondria, aggregates, and soluble fraction of NDUFA11 KO and WT HEK293T cells

ABSTRACT: Perturbed proteostasis and mitochondrial dysfunction are often associated with age-related diseases such as Alzheimer’s and Parkinson’s diseases. However, the link between them remains incompletely understood. Mitochondrial dysfunction causes proteostasis imbalance, and cells respond to restore proteostasis by increasing proteasome activity and molecular chaperons in yeast and C. elegans. Here, we demonstrate the presence of similar responses in humans. Mitochondrial dysfunction upregulates a small heat shock protein HSPB1 and an immunoproteasome subunit PSMB9 leading to an increase in proteasome activity. HSPB1 and PSMB9 are required to prevent protein aggregation upon mitochondrial dysfunction. Moreover, PSMB9 expression is dependent on a translation elongation factor EEF1A2, and PSMB9-containing proteasomes are located near mitochondria, enabling fast local degradation of aberrant proteins. Our findings put a step forward in understanding the stress response triggered by mitochondrial dysfunction, and may be useful for therapeutic strategies to prevent or delay the onset of age-related diseases and attenuate their progression.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hek-293t Cell

SUBMITTER: Remigiusz Serwa

LAB HEAD: Prof. Agnieszka Chacinska

PROVIDER: PXD038004 | Pride | 2023-07-03

REPOSITORIES: Pride

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			Action	DRS
	PE_aggregates_fr1i2i3.raw	Raw
	PE_aggregates_fr4i5i6.raw	Raw
	PE_aggregates_fr7i8.raw	Raw
	PE_cytosol_fr1.raw	Raw
	PE_cytosol_fr2.raw	Raw

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Shotgun analysis of proteins in NDUFA11 KO and WT HEK 293T cells.

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