Mitochondrial Fusion

Mitochondria, dubbed the ‘powerhouse of the cell’, are a type of organelle present in most human cells. Their primary function is to generate Adenosine Triphosphate (ATP), the cell’s principal source of chemical energy. Unlike most other organelles, mitochondria store their own set of genetic material, distinct from the DNA situated in a cell’s nucleus. Although this ‘mitochondrial genome’ represents only 0.1% of a cell’s genetic information, it often plays a significant role in development.

A. SIGNIFICANCE. Our goal is to screen chemical libraries to identify compounds that modulate mitochondrial transport in hippocampal and cortical neurons. This study is significant in four ways: (1) There is an urgent need to develop CNS (Central Nervous System) active drugs. CNS disorders are not only staggeringly complex but are poorly treated diseases (Palmer and Stephenson, 2005). In the United States alone the annual cost for stroke, depression, Schizophrenia and Alzheimer’s disease are currently estimated to be over $250 billion annually (Pangalos et al., 2007). Despite the advances in translational medicine and pharmaceutical research little progress has been made in developing CNS therapeutics. Improving CNS drug discovery efforts is an urgent goal as an estimated 1.5 billion people suffer from CNS-related diseases worldwide. Unfortunately only a handful of new drugs have been brought to the market with very few in the pharmaceutical pipeline (Kissinger, 2011; Schoepp, 2011; Abbot, 2011). The majority of pharmaceutical companies have recently announced a shift from supporting internal drug discovery efforts in favor of academic and government partnerships (Schoepp, 2011). At Scripps Florida we have close interaction of state of the art high throughput small molecule screening and cutting-edge neuroscience research. Thus we are in a unique position to address the challenges in developing CNS therapeutics. (2) Mitochondrial dysfunction is part of the pathophysiology of

Under normal conditions, the mitochondria maintain cytosolic Ca2+ levels, which is necessary for normal cellular function. However, the mitochondrial uptake of excessive levels of Ca2+ can lead to inhibition of ATP synthesis, disruption of mitochondrial membrane potential, increased ROS production, and generation of the mitochondrial permeability transition (mPT) state, which is thought to occur in response to formation of the mPT pore. As a consequence, cellular demise can occur through necrotic-related mechanisms events, including a loss of energy production and oxidative stress as well as apoptotic-related mechanisms, including the mitochondrial release of pro-apoptotic proteins. Given the central role of the mitochondria in cell

Presbycusis or Age-related hearing impairment is the most frequent sensory disorder in the adults. It affects more than half of all adults by age seventy-five years. Presbycusis is an irreversible symmetrical progressive loss of hearing sensitivity during the lifespan. It has an insidious onset without clinical manifestation so detected by the routine diagnostic test after losing or damaging to inner ear cells and neurons. Presbycusis counted as an untreatable disorder since these inner ear structures lose the ability of regeneration. Mitochondria by production reactive oxygen species or inducing apoptotic genes is one of most prominent intracellular organelles that contribute in presbycusis progression. The present study focused on mitochondrial

Many physiological processes in the cells require the participation of both intra- and extra-mitochondrial enzyme reactions. A link between mitochondria and cytosol is provided by a group of proteins known as the mitochondrial carriers (MCs) family (Arco & Satrustegui, 2005; F. Palmieri, 2004). MCs comprise a family of about 40-50 proteins, depending on the organism, and provide the main communication between mitochondrial matrix and extra-mitochondrial spaces by transporting a wide range of metabolites, nucleotides and cofactors.

The former are transmitted by maternal inheritance, while the latter have Mendelian inheritance. Most individuals with Leigh’s syndrome have an autosomal recessive or X-linked disorder of mitochondrial energy generation rather than an mtDNA mutation (Thorburn and Rahman 2003). Leigh’s syndrome arises mainly due to “dysfunction of the mitochondrial respiratory chain” (Chinnery 2000). An important cause of Leigh’s syndrome is “mutations in the complex IV assembly genes, particularly SURF1” (Lee et al. 2012). The SURF1 gene is found in nuclear DNA and is located on the long arm of chromosome 9. The gene defect in Leigh’s syndrome has been mapped to chromosome 9q34. SURF1 belongs to a family of genes called mitochondrial respiratory chain assembly factors and encodes a protein restricted to the inner membrane of the mitochondria. This SURF1 protein contains a unique mitochondrial targeting sequence at its N-terminus. The main function of SURF1 is to encode a factor involved in the biogenesis of the cytochrome c oxidase complex (Zhu et al.

The hypoxia-inducible factor prolyl hydroxylase domain enzymes (HIF-PHDs) are a family of oxygen sensors that has been implicated in neuronal survival. Catalysis by the HIF-PHDs destabilizes the transcriptional activator HIF-1a under normoxia. HIF-PHDs are promising target candidates for mitochondrial protection in paradigms of oxidative stress. The inhibition of HIF-PHDs prevented neuronal cell death induced by mitochondrial toxins [1][2].

Mitochondrial fission requires dynamin-related protein 1 (Drp1). Drp1 is a large GTPase that can assemble into oligomers with enhanced GTPase activity. Drp1 is predominantly located in the cytosol and can be recruited to mitochondria to mediate mitochondrial fission by forming an oligomeric ring around the mitochondrial tubule to constrict and sever mitochondrial outer membranes 38-43. Having found that dysbindin-1 regulates mitochondrial fission, we proceeded to test whether dysbindin-1 is involved in the association of Drp1 with mitochondria. Cultured hippocampal neurons (DIV14) were transfected with the mitoDsRed plasmid along with the dysbindin-1 siRNAs, scrambled siRNAs, dysbindin-1C or -1A

“The world’s first baby to be born from a new procedure that combines the DNA of three people appears...” The online article “DNA of Three People” discusses a procedure and case study of a mitochondrial transfer in Mexico. A young woman carries the genes for the fatal Leigh syndrome and is unable to have healthy children. After having three miscarriages and losing three children, due to the syndrome, she finally reached out to Dr. John Zhang.

The mitochondria is an essential organelle that produces energy for the cell. It has many functions, but the most important is that it converts monosaccharides, like glucose, and oxygen into ATP through cellular respiration. It also gives energy to motile cells like muscles so they can move. The structure of the mitochondria consists of a double phospholipid bilayer membrane. There is an outer membrane and an inner membrane. They both, along with cristae, increase the cell’s surface area and productivity. Mitochondria also separate the intermembrane space and mitochondrial matrix, the location where cell respiration occurs because of the high amount of enzymes. They replicate and grow within cell but reproduce through fission which is when

Mitochondrial myopathy is a disease of the muscles caused by changes in the mitochondria often connected with excess lipid build up, the brain and muscles require a lot of energy therefore these tissues may seem damaged or dysfunctional if the mitochondria is morphed. This disorder is most commonly identified

After cytosolic release from macropinosomes, MITO-Porters translocate into the mitochondrial membrane through electrostatic interaction between the MITO-Porters and mitochondria and induce fusion(56). The lipid composition of the MITO-Porter promotes both fusion with the mitochondrial membrane and releases of its cargo to the intra-mitochondrial compartment(33). MITO-Porter encapsulating propidium iodide (a fluorescent dye used to stain nuclei) could successfully deliver propidium iodide to the mitochondrial

The mitochondria is referred to as a “powerhouse” of a certain cell. This membrane bound organelles main job is to perform cellular respiration, which in simple terms, is when it breaks down diffused nutrients into usable energy for the whole cell. Adding on to that, the mitochondria also contributes to the making of ATP (Adenosine Triphosphate) by providing 3% of its genes for it. ATP is basically a complex nanomachine that provides a “primary energy currency” for a cell.

Supplementary Figure 1. Mitochondria are elongated in sdy mice. Hippocampal slices cultured from sdy mice and their WT littermates were transduced with lentivirus expressing mitoDsRed. Histograms show cumulative probabilities of mitochondrial length in WT and sdy slices.

Mitochondria are rod-shaped organelles that can be considered the powerhouse of the cell. Mitochondria generate chemical energy in the form of adenosine triphosphate by metabolizing sugars, fats, and other chemical fuels with the assistance of molecular oxygen in a process called aerobic respiration and mitochondria enable cells to produce 15 times more ATP than they could otherwise. The number of mitochondria present in a cell depends upon the metabolic requirements of that cell, and may range from a single large mitochondrion to thousands of them. mitochondria are different from most organelles because they have their own DNA and reproduce independently. In most animal species, mitochondria appear to be inherited through the