GenProMarkers™, Inc.

Microarray, Bioinformatics and Systems Biology for Discovery of Gene and Protein Biomarkers

Frequently Asked Questions

Q: Why using hMitChip3 to study neuroendocrine (including eyes) disease/disorder?
A: Mitochondrial function in brain is of particular importance because of its high energy demand.  Ninety percent (90%) of the cell energy (ATP) are generated via mitochondrial oxidative phosphorylation pathways.  Although human brain represents only 2% of body weight, it receives 15% of the body’s cardiac output and consumes 20% of total body oxygen.  These high level oxygen and energy requirements are continuous and imply that even brief periods of oxygen or glucose deprivation may impair neuron function and even result in neuron death.  The above mentioned features of hMitChip3 make it a perfect high-throughput genomic tool for hypothesis-driven and hypothesis-generation studies of brain disease/disorder.


Q: Why using hMitChip3 to study obesity and diabetes?
A: Mitochondria are essential for ATP synthesis via oxidative phosphorylation (OXPHOS) and their dysfunction may cause energy deficiency in cells resulting in metabolic disorders: obesity and diabetes.  Obesity or excessive bodyweight with elevated free fatty acids in the blood stream affects 2.1 billion people worldwide, and one of its adverse consequences is type 2 diabetes mellitus (T2DM). T2DM is characterized by hyperglycemia resulting from insufficient production of insulin by pancreatic β-cells, and insulin resistance in target tissues (muscle, liver and fat). Lipotoxicity and glucotoxicity in obesity and T2DM induce the β-cell overexpression of uncoupling protein 2 which increases proton leakage across the mitochondrial inner membrane and decreases ATP synthesis leading to insufficient secretion of insulin.  Moreover, insulin resistance in the target tissues has been related to the decreased mitochondrial content, reduced fatty acid oxidation, defective OXPHOS, and poor ATP production.  hMitChip3 and its related bioinformatic tool offer the specific and affordable high-throughput means for screening the patient population and leading to individualized medicine!

 Mitochondrial OXPHOS and ATP production. Lipids and carbohydrates fuel the respiratory chain (complex I to V) on the mitochondrial inner membrane. Acetyl-CoA from degradation of glucose or fatty acids is further oxidized in the TCA cycle, producing CO2 and reducing equivalents such as NADH and FADH2. These reducing equivalents provide electrons to the respiratory chain upon their reoxidation. An electronchemical gradient is established by pumping protons from the matrix across the inner membrane through complex I, III and IV, and is used for synthesis of ATP from ADP and Pi by complex V (ATP synthase). Reactive oxygen species (ROS) is by-products of ATP generation and induces mtDNA mutations and protein damage. High ROS may induce apoptosis. UCP2, uncoupling protein 2; ANT, adenine nucleotide translocator.

Mechanism of glucose-stimulated insulin release in pancreatic β-cells. Under normal conditions, glucose is transported into β-cell, phosphorylated by glucokinase and converted to pyruvate via glycolysis. Pyruvate is shuttled into mitochondria and activates the TCA cycle, resulting in the transfer of reducing equivalents to the respiratory chain and ATP generation. An increase in the ATP/ADP ratio leads to closing of ATP-controlled potassium channels (KATP), cell membrane depolarization and opening of voltagegated calcium (Ca2+) channel. The raised cytosolic Ca2+ concentration triggers insulin excytosis and therefore, secretion.  In obesity, free fatty acids (FFA) and hyperglycemia induce overexpression of uncoupling protein 2 (UCP2) and superoxide (O2-). The former increases the proton leak across mitochondrial inner membrane, and diverts electrochemical potential away from ATP synthesis. The latter activates UPC2 activity, worsens ATP production, promotes apoptosis and therefore, impaired insulin secretion by β-cells.


 Q: Why using hMitChip3 to study Cancer (Warburg effect)?
A: Mitochondrial oxidative phosphorylation pathways provide the normal cell with 90% energy (ATP), while most cancer cells predominantly produce energy by glycolysis followed by lactic acid fermentation in the cytosol, rather than by oxidation of pyruvate in their mitochondria (Warburg effect).  In addition, reactive oxygen species, an inevitable by-product of mitochondrial oxidative phosphorylation, can damage DNA and proteins and have been implicated in cancers.  Furthermore, mitochondria play a vital role in programmed cell death (apoptosis) which is involved in development of cancers and the resistance to cancer therapy.  Thus, hMitChip3 is an excellent high-throughput genomic tool for hypothesis-driven study of cancer.


Q: Why using hMitChip3 to study Anti-apoptosis, anti-oxidation and pro-apoptosis?
A: Mitochondrial oxidative phosphorylation pathways generate 90% cellular energy (ATP).  The high energy production is coupled with the inevitable production of a high level of reactive oxygen species, that cause DNA and protein damage and have implications in cancer, as well as neurodegenerative diseases and aging.  Also, the mitochondrial membrane permeability plays a vital role in apoptosis.  Therefore, hMitChip3 is a cost-effective high-throughput genomic and bioinformatic tool for the identification of dysregulated anti-apoptotic, anti-oxidative and pro-apoptotic genes.


Q: Why using hMitChip3 to study Chronic fatigue?
A: Mitochondrial abnormalities in patients with chronic fatigue are well documented.  Because the function of mitochondria in producing ATP, the energy currency for all body functions, and recycling ADP to replenish the ATP supply determine the energetic activities and levels of the cells and individuals, the examination of mitochondrial function, oxidative phosphorylation pathways, ATP production, transferring efficiencies of ADP into the mitochondria and ATP into the cytosol is essential to study chronic fatigue and requires efficient genomic and proteomic tools.  The hMitChip3 gene chip and related bioinformatics software provide investigators with the high throughput means to profile a holistic rather than a piecemeal fingerprint of mitochondrial transcriptomes and therefore functions.  hMitChip3 can differentiate cells and individuals with energy-deficiency in specific molecular pathways and therefore the resultant specific knowledge may be useful for remedial actions, in the form of dietary supplements, drugs and detoxification.


Q: Why using hMitChip3 to study pharmacogenomics?
A: Mitochondria at the intersection of many molecular pathways are a central target of diverse pharmacological agents.  Many drugs have direct effects on mitochondrial ultra-structure and function.  The hMitChip3 and related bioinformatics tools are customized high-throughput tools for pharmacogenomics research.


Q: Why using hMitChip3 to study toxicity?
A: Mitochondria at the intersection of many molecular pathways are a central target of diverse pharmacological agents.  Many drugs have direct effects on mitochondrial ultra-structure and function.  The hMitChip3 and related bioinformatics tools are customized high-throughput tools for toxicity of drugs.