Immunoelectron microscopy provides evidence for the presence of mitochondrial heat shock 10-kDa protein (chaperonin 10) in red blood cells and a variety of secretory granules

Abstract

Hsp10 (10-kDa heat shock protein, also known as chaperonin 10 or Cpn10) is a co-chaperone for Hsp60 in the protein folding process. This protein has also been shown to be identical to the early pregnancy factor, which is an immunosuppressive growth factor found in maternal serum. In this study we have used immunogold electron microscopy to study the subcellular localization of Hsp10 in rat tissues sections embedded in LR Gold resin employing polyclonal antibodies raised against different regions of human Hsp10. In all rat tissues examined including liver, heart, pancreas, kidney, anterior pituitary, salivary gland, thyroid, and adrenal gland, antibodies to Hsp10 showed strong labeling of mitochondria. However, in a number of tissues, in addition to the mitochondrial labeling, strong and highly specific labeling with the Hsp10 antibodies was also observed in several extramitochondrial compartments. These sites included zymogen granules in pancreatic acinar cells, growth hormone granules in anterior pituitary, and secretory granules in PP pancreatic islet cells. Additionally, the mature red blood cells which lack mitochondria, also showed strong reactivity with the Hsp10 antibodies. The observed labeling with the Hsp10 antibodies, both within mitochondria as well as in other compartments/cells, was abolished upon omission of the primary antibodies or upon preadsorption of the primary antibodies with the purified recombinant human Hsp10. These results provide evidence that similar to a number of other recently described mitochondrial proteins (viz., Hsp60, tumor necrosis factor receptor-associated protein-1, P32 (gC1q-R) protein, and cytochrome c), Hsp10 is also found at a variety of specific extramitochondrial sites in normal rat tissue. These results raise important questions as to how these mitochondrial proteins are translocated to other compartments and their possible function(s) at these sites. The presence of these proteins at extramitochondrial sites in normal tissues has important implications concerning the role of mitochondria in apoptosis and genetic diseases.

Mitochondrial proteome analysis reveals altered expression of voltage dependent anion channels in pancreatic β-cells exposed to high glucose

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Effects of intrinsic aerobic capacity, aging and voluntary running on skeletal muscle sirtuins and heat shock proteins

“…Though originally identified as a mitochondrial chaperone, Hsp10 is also known to be present in cytosol, cell surface, extracellular space and peripheral blood and to have various other cellular functions (Jia et al, 2011;Sadacharan et al, 2001). The ability of HSP10 to change its location is believed to be related to the protection of cells from various kinds of stressors such as infections and inflammation that are potential threats for healthy aging (Jia et al, 2011).…”

Mitochondrial chaperones in cancer: From molecular biology to clinical diagnostics

“…Although in normal cells Hsp10 is localized mostly in the mitochondrial matrix, it has also been found in other sub-cellular localizations, such as zymogene granules, hormone granules, secretory granules and mature red blood cells. 48 For many years Hsp10 has been mostly considered a partner of Hsp60 in the Hsp60/10 protein folding machine. Chaperonin complex structure was resolved at high resolution, and detailed descriptions of the chaperonin mediated folding cycle have been proposed by different research groups.…”