ORGANELLE MARKERS - Mitochondria

VDAC

The Voltage-Dependent Anion Channel (VDAC or mitochondrial Porin) is an outer membrane mitochondrial protein. The VDAC protein is thought to form the major pores through which adenine nucleotides are transferred through the outer mitochondrial membrane.

VDAC has also been implicated in the formation of the mitochondrial permeability transition pore complex in apoptotic cells. This complex, formed by VDAC, adenine nucleotide translocator (ANT), and cyclophilin D (CypD), is thought to allow the mitochondria to undergo metabolic uncoupling and irreversible morphologic changes that ultimately destroy the mitochondria during apoptosis.

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TOMM22

A preprotein is stably arrested and accumulated in the GIP complex by Tom40 and Tom22.4 Such a 100 kDa core complex probably contains a single channel that retains the basic channel properties but is already open in the absence of preproteins. In contrast, in the presence of Tom22, the wild-type GIP complex contains tightly regulated channels (probably three channels). Tom22 apparently represents a component of the machinery that controls the gate. The cytosolic domains of Tom22 and Tom20 are believed to form the major part of a cis site, which mediates the import of all preproteins known to use the general import machinery of mitochondria. The preprotein is then routed through the Tom complex translocation channel and transferred to a trans site on the intermembrane space (IMS) side of the outer membrane. The inter-membrane space exposed segment of Tom40 and the C-terminal tail of Tom22 may contribute to the trans-site. Matrix-targeted proteins are further transferred to the matrix through Product Information import machinery in the inner membrane.

The TOM complex of mammalian mitochondria resembles the fungal Tom complex, but is distinct from the plant TOM system. Thus, while unique components of the mammalian mitochondrial import system have been identified (e.g. TOM34 and metaxin), Tom22, and Tom37 have not been identified in plant mitochondria.

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Hsp70

In response to adverse changes in their environment, cells from many organisms increase the expression of a class of proteins referred to as heat shock or stress proteins. One class of stress proteins, termed the Hsp70 family, is comprised of multiple members, all of which bind ATP in vitro, but which are localized within different intracellular compartments. These include: i) Hsc70 (or constitutive form) present within the cytosol/nucleus; ii) Hsp70 (inducible form) present within the cytosol/nucleus/nucleolus; iii) the constitutive glucose-regulated 78 kDa (or BiP) protein present within the lumen of the endoplasmic reticulum; and iv) the constitutive glucose regulated 75 kDa protein present within the mitochondrial matrix. Members of the Hsp70 family are thought to function as molecular chaperones, assisting in the folding of other proteins in various intracellular compartments. Grp75 is localized in the mitochondrial matrix, where, in concert with Hsp60, is thought to participate in the re-folding of proteins translocated into this organelle. Like its E. coli homolog DnaK, Grp75 possesses a cation-dependent ATPase activity thought to be central to its function as a chaperone.

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Hsp60

The Hsp60 of Heliothis viescens is a member of a highly conserved family which includes molecular chaperones from several species such as plant Hsp60 (known as Rubisco binding protein), GroEL, the E.coli Hsp60 and 65 kDa major antigen of mycobacteria. In eukaryotes, Hsp60 is localized in the mitochondrial matrix and in plants Hsp60 is localized in the chloroplast. Mitochondria, chloroplasts and bacteria have a common ancestry (>1billion years) and this fact together with the high degree of homology between the divegent Hsp60s would indicate that these proteins carry out a primitive but important function which is similar to all of these different species. The common characteristics of the Hsp60s from the divergent species are i) high abundance, ii) induction with environmental stress such as heat shock, iii) homo-oligomeric structures of either 7 or 14 subunits which reversibly dissociate in the presence of Mg2+ and ATP, iv) ATPase activity and v) a role in folding and assembly of oligomeric protein structures. These similarities are supported by recent studies where the single-ring human mitochondrial homolog, Hsp60 with its co-chaperonin, Hsp10 were expressed in a E. coli strain, engineered so that the groE operon is under strict regulatory control. This study has demonstrated that expression of Hsp60-Hsp10 was able to carry out all essential in vivo functions of GroEL and its co-chaperonin, GroES. Consistent with their functions as chaperones, Hsp60 and Hsp10 have been suggested to act as docking molecules with a passive role in the maturation of caspase processing. Data demonstrates that recombinant Hsp60 and Hsp10 have been shown to accelerate the activation of procaspase-3 by cytochrome c and dATP in an ATP-dependent manner. Hsps are intracellular proteins which are thought to serve protective functions against infection and cellular stress, however several recent studies indicate that members of the Hsp60 family are linked to a number of autoimmune diseases, artherosclerosis and chlamydial disease.

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Superoxid dismutase (SOD)

Superoxide dismutase (SOD) is responsible for the elimination of cytotoxic active oxygen by catalyzing the dismutation of the superoxide radical to oxygen and hydrogen peroxide. There are three SOD isoenzymes in mammalian cells. They are: extracellular SOD (EC SOD), copper and zinc-containing SOD (Cu/Zn SOD) and manganese-containing SOD (Mn SOD). The Cu/Zn form contains Cu and Zn ions and exists as a 32 kDa dimer in the cytosol. Mn SOD is an 80 kDa tetramer that contains Mn ion and resides in the mitochondrial matrix. Mn SOD is a tumor necrosis factor (TNF)- inducible enzyme that protects cells from TNF-mediated apoptosis via superoxide anion detoxification and the subsequent regulation of apoptosis through cytochrome c release and the modulation of the redox state of the mitochondria. Mn SOD has also been shown to be a tumor suppressor in human breast cancer. Overexpression of this enzyme protects neurons from NMDA- and nitric oxide-induced neurotoxicity.

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UCP1

Mitochondrial oxidative phosphorylation makes possible ATP synthesis using the energy available from substrate oxidation at the respiratory chain. These processes are coupled through the proton electrochemical potential gradient generated during the transfer of electrons from the substrate to oxygen. The uncoupling proteins (UCPs) are mitochondrial inner membrane proteins that are considered to be transporters functioning as enzymatic uncouplers of oxidative phosphorylation. They are capable of returning protons pumped by the respiratory chain to the mitochondrial matrix. Uncoupling proteins currently comprise UCP1, UCP2, UCP3, UCP4, and UCP5. UCP1 is a 32 kDa protein that is active as a proton channelforming dimer. It can bind purine nucleotides and is capable of being stimulated by fatty acids. Proton transport by UCP1 has been shown to depend on CoQ (ubiquinone) as an obligatory cofactor. UCP1 is exclusively expressed in BAT in rodents and in neonates where it is regulated by norepinephrine and thyroid hormones. Stimulated BAT is able to dissipate energy as heat via uncoupled mitochondrial respiration. The liberated heat can serve several physiological functions, e.g. for body heating during emergence from hibernation or during cold exposure, for burning body fat and consequently for body weight regulation.

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UCP2

Mitochondrial oxidative phosphorylation makes possible ATP synthesis using the energy available from substrate oxidation at the respiratory chain. These processes are coupled through the proton electrochemical potential gradient generated during the transfer of electrons from the substrate to oxygen. The uncoupling proteins (UCPs) are mitochondrial inner membrane proteins that are considered to be transporters functioning as enzymatic uncouplers of oxidative phosphorylation. They are capable of returning protons pumped by the respiratory chain to the mitochondrial matrix. Uncoupling proteins currently comprise UCP1, UCP2, UCP3, UCP4, and UCP5. UCP1 is a 32 kDa protein that is active as a proton channelforming dimer. It can bind purine nucleotides and is capable of being stimulated by fatty acids. Proton transport by UCP1 has been shown to depend on CoQ (ubiquinone) as an obligatory cofactor. UCP1 is exclusively expressed in BAT in rodents and in neonates where it is regulated by norepinephrine and thyroid hormones. Stimulated BAT is able to dissipate energy as heat via uncoupled mitochondrial respiration. The liberated heat can serve several physiological functions, e.g. for body heating during emergence from hibernation or during cold exposure, for burning body fat and consequently for body weight regulation.

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UCP3

Mitochondrial oxidative phosphorylation makes possible ATP synthesis using the energy available from substrate oxidation at the respiratory chain. These processes are coupled through the proton electrochemical potential gradient generated during the transfer of electrons from the substrate to oxygen. The uncoupling proteins (UCPs) are mitochondrial inner membrane proteins that are considered to be transporters functioning as enzymatic uncouplers of oxidative phosphorylation. They are capable of returning protons pumped by the respiratory chain to the mitochondrial matrix. Uncoupling proteins currently comprise UCP1, UCP2, UCP3, UCP4, and UCP5. UCP1 is a 32 kDa protein that is active as a proton channelforming dimer. It can bind purine nucleotides and is capable of being stimulated by fatty acids. Proton transport by UCP1 has been shown to depend on CoQ (ubiquinone) as an obligatory cofactor. UCP1 is exclusively expressed in BAT in rodents and in neonates where it is regulated by norepinephrine and thyroid hormones. Stimulated BAT is able to dissipate energy as heat via uncoupled mitochondrial respiration. The liberated heat can serve several physiological functions, e.g. for body heating during emergence from hibernation or during cold exposure, for burning body fat and consequently for body weight regulation.

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Prohibitin

Prohibitin is an evolutionarily conserved protein located in the inner membrane of mitochondria. Prohibitin shows antiproliferative activity and has been proposed to play a role in normal cell cycle regulation, replicative senescence, cellular immortalization and tumor suppression.

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Mitochondria

The antibodies shows specific reactivity to a mitochondrial antigen. Stains mitochondria in all human cell types.

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