Intracellular Disposition of Mitochondrial Molecular Chaperones: Hsp60, mHsp70, Cpn10 and TRAP-1

Gupta, Radhey S.; Bowes, Timothy; Sadacharan, Skanda; Singh, Bhag

doi:10.1017/cbo9780511546310.003

Cited by 2 publications

(4 citation statements)

References 75 publications

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“…By contrast, the labelling in other cell compartments such as the nucleus was generally weak, near background levels. These observations for Hsp10 were similar to those that had been reported earlier for Hsp60 [ 42 ].…”

Section: Discussionsupporting

confidence: 92%

Hsp10 nuclear localization and changes in lung cells response to cigarette smoke suggest novel roles for this chaperonin

et al. 2014

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Heat-shock protein (Hsp)10 is the co-chaperone for Hsp60 inside mitochondria, but it also resides outside the organelle. Variations in its levels and intracellular distribution have been documented in pathological conditions, e.g. cancer and chronic obstructive pulmonary disease (COPD). Here, we show that Hsp10 in COPD undergoes changes at the molecular and subcellular levels in bronchial cells from human specimens and derived cell lines, intact or subjected to stress induced by cigarette smoke extract (CSE). Noteworthy findings are: (i) Hsp10 occurred in nuclei of epithelial and lamina propria cells of bronchial mucosa from non-smokers and smokers; (ii) human bronchial epithelial (16HBE) and lung fibroblast (HFL-1) cells, in vitro, showed Hsp10 in the nucleus, before and after CSE exposure; (iii) CSE stimulation did not increase the levels of Hsp10 but did elicit qualitative changes as indicated by molecular weight and isoelectric point shifts; and (iv) Hsp10 nuclear levels increased after CSE stimulation in HFL-1, indicating cytosol to nucleus migration, and although Hsp10 did not bind DNA, it bound a DNA-associated protein.

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Section: Discussionsupporting

confidence: 92%

Hsp10 nuclear localization and changes in lung cells response to cigarette smoke suggest novel roles for this chaperonin

et al. 2014

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“…The extramitochondrial presence of the mit-DNA encoded proteins (Gingrich et al 2004;Sadacharan et al 2005), which are transcribed and translated within the organelle, provide compelling evidence that there exists a mechanism(s) in cells by which proteins can be translocated or transported from mitochondria to other speciWc cellular destinations. Many of these proteins (NADH dehydrogenase subunit I and II, mAspAT, P32/gC1qR/ HABP-1, TRAP-1, Cpn10, Hsp60, mit-Hsp70) carry out unique biochemical functions at these ectopic sites, which are quite diVerent from their known mitochondrial functions (Bruschi et al 1993;Xu et al 1994;Jones et al 1994;Cavanagh and Morton 1994;Khan et al 1998;Soltys and Gupta 1999;Bradbury and Berk 2000;Ran et al 2000;Ranford et al 2000;Ghebrehiwet et al 2001;Maguire et al 2002;Kaul et al 2003;Gingrich et al 2004;Gupta et al 2005;Henderson and Pockley 2005;Deocaris et al 2006). This strongly suggests that the presence of these proteins at speciWc extramitochondrial sites is not an artifact, but instead serves important physiological functions at these locations.…”

Section: Discussionmentioning

confidence: 99%

“…More work into understanding the mechanism of the ectopic localization of mit-proteins and the possible functions that they carry out at these locations will undoubtedly shed light on these issues. These studies should prove of great importance in clarifying the role of mitochondria and mitochondrial proteins in diverse cellular processes (Soltys and Gupta 1999;Gupta et al 2005).…”

Section: Discussionmentioning

confidence: 99%

“…NADH dehydrogenease subunits 1 and 2, cytochrome c oxidase (COX) subunits I and II and ATP synthase subunit 6) (Loveland et al 1990;Gingrich et al 2004;Sadacharan et al 2005), which are present at extramitochondrial locations have been discovered. A number of these proteins carry out unique functions at these ectopic locations which are diVerent from those in mitochondria (Loveland et al 1990;Isola et al 1995;Cavanagh 1996;Bradbury and Berk 2000;Ran et al 2000;Gingrich et al 2004;Gupta et al 2005). The mechanism(s) responsible for extramitochondrial localization of these proteins remains to be elucidated (Poyton et al 1992;Smalheiser 1996;Soltys and Gupta 1999;Mueller et al 2004).…”

Section: Introductionmentioning

confidence: 99%

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Subcellular localization of fumarase in mammalian cells and tissues

Bowes

Singh

Gupta

2006

Histochem Cell Biol

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Fumarase, a mitochondrial matrix protein, is previously indicated to be present in substantial amounts in the cytosol as well. However, recent studies show that newly synthesized human fumarase is efficiently imported into mitochondria with no detectable amount in the cytosol. To clarify its subcellular localization, the subcellular distribution of fumarase in mammalian cells/tissues was examined by a number of different methods. Cell fractionation using either a mitochondria fraction kit or extraction with low concentrations of digitonin, detected no fumarase in a 100,000 g supernatant fraction. Immunofluorescence labeling with an affinity-purified antibody to fumarase and an antibody to the mitochondrial Hsp60 protein showed identical labeling pattern with labeling seen mainly in mitochondria. Detailed studies were performed using high-resolution immunogold electron microscopy to determine the subcellular localization of fumarase in rat tissues, embedded in LR White resin. In thin sections from kidney, liver, heart, adrenal gland and anterior pituitary, strong and specific labeling due to fumarase antibody was only detected in mitochondria. However, in the pancreatic acinar cells, in addition to mitochondria, highly significant labeling was also observed in the zymogen granules and endoplasmic reticulum. The observed labeling in all cases was completely abolished upon omission of the primary antibody indicating that it was specific. In a western blot of purified zymogen granules, a fumarase-antibody cross-reactive protein of the same molecular mass as seen in the mitochondria was present. These results provide evidence that fumarase in mammalian cells/tissues is mainly localized in mitochondria and significant amounts of this protein are not present in the cytosol. However, these studies also reveal that in certain tissues, in addition to mitochondria, this protein is also present at specific extramitochondrial sites. Although the cellular function of fumarase at these extramitochondrial locations is not known, the appearance/localization of fumarase outside mitochondria may help explain how mutations in this mitochondrial protein can give rise to a number of different types of cancers.

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Intracellular Disposition of Mitochondrial Molecular Chaperones: Hsp60, mHsp70, Cpn10 and TRAP-1

Cited by 2 publications

References 75 publications

Hsp10 nuclear localization and changes in lung cells response to cigarette smoke suggest novel roles for this chaperonin

Hsp10 nuclear localization and changes in lung cells response to cigarette smoke suggest novel roles for this chaperonin

Subcellular localization of fumarase in mammalian cells and tissues

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