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Ablation of the mitochondrial complex IV assembly protein Surf1 leads to increased expression of the UPR(MT) and increased resistance to oxidative stress in primary cultures of fibroblasts.

Abstract：

:Mice deficient in the electron transport chain (ETC) complex IV assembly protein SURF1 have reduced assembly and activity of cytochrome c oxidase that is associated with an upregulation of components of the mitochondrial unfolded protein response (UPR(MT)) and increased mitochondrial number. We hypothesized that the upregulation of proteins associated with the UPR(MT) in response to reduced cytochrome c oxidase activity in Surf1(-/-) mice might contribute to increased stress resistance. To test this hypothesis we asked whether primary cultures of fibroblasts from Surf1(-/-) mice exhibit enhanced resistance to stressors compared to wild-type fibroblasts. Here we show that primary dermal fibroblasts isolated from Surf1(-/-) mice have increased expression of UPR(MT) components ClpP and Hsp60, and increased expression of Lon protease. Fibroblasts from Surf1(-/-) mice are significantly more resistant to cell death caused by oxidative stress induced by paraquat or tert-Butyl hydroperoxide compared to cells from wild-type mice. In contrast, Surf1(-/-) fibroblasts show no difference in sensitivity to hydrogen peroxide stress. The enhanced cell survival in response to paraquat or tert-Butyl hydroperoxide in Surf1(-/-) fibroblasts compared to wild-type fibroblasts is associated with induced expression of Lon, ClpP, and Hsp60, increased maximal respiration, and increased reserve capacity as measured using the Seahorse Extracellular Flux Analyzer. Overall these data support a protective role for the activation of the UPR(MT) in cell survival.

journal_name

Redox Biol

journal_title

Redox biology

authors

Pharaoh G,Pulliam D,Hill S,Sataranatarajan K,Van Remmen H

doi

10.1016/j.redox.2016.05.001

subject

Has Abstract

pub_date

2016-08-01 00:00:00

pages

430-8

issn

2213-2317

pii

S2213-2317(16)30030-1

journal_volume

8

pub_type

杂志文章

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