"Understanding the molecular machinery that helps distribute mitochondria to different parts of the cell has only recently begun to be understood," said University of Rochester Medical Center neurologist David Rempe, M.D., Ph.D., the lead author of the study.
"We know that in some disease states that mitochondria function is modified, so understanding how their activity is modulated is important to understanding how the brain responds to a pathological state."
Mitochondria are cellular power plants that generate most of the cell's supply of adenosine triphosphate (ATP), which is used as a source of chemical energy. While mitochondria are present in all of the body's cells, some cells – because of their size and purpose – need to transport mitochondria to distant sites within the cell to maintain proper function. A prominent example is neurons which have a complex cellular structure that consist of a main cell body and dendrites and axons that project out from the cell core and transmit signals to adjoining cells via synapses at their terminus.
"Neurons are at a disadvantage in terms of their anatomy," said Rempe. "They put out enormous arms of axons and dendrites and they have to keep supplying nutrients and everything down these arms. The supply line is very long."
The supply line includes mitochondria which the cell must also push down the axons and dendrites to provide these parts of the cell with energy, help with the transmission of signals, and generally maintain cellular health. Mitochondria are constantly cycling throughout the neuron. Some are stationary while others are moving down the arms of the cell to assume their proper position. Additionally, for reasons not completely understood, at any given time about half of the mobile mitochondria in the neuron are in the process of returning to the cell body – perhaps to be recycled or replenished in some form.
Rempe and his colleagues have discovered a protein that plays a critical role in regulating the movement – or transport – of mitochondria in neuron cells. The protein, which they dubbed hypoxia upregulated mitochondrial movement regulator (HUMMR), is produced in a state of low oxygen called hypoxia. HUMMR is induced by another protein called hypoxic inducible factor 1 alpha (HIF-1) which is responsible for triggering several processes in the cell that help it function in a low oxygen environment.
The primary role of HUMMR is to regulate the proper transport and distribution of mitochondria throughout the cell, essentially ensuring that they are in the correct position. One of the ways that the University of Rochester team was able to determine this is that when HUMMR was expressed at lower than normal levels, they observed that a greater number of the mitochondria began to abandon their posts along the cell's dendrites and axon and return to the cell body proper.
Understanding the mechanisms that regulate the movement of mitochondria may help scientists identify how the brain's cells ward off and potentially repair damage. An example is the role that mitochondria play as a calcium buffer. One of the mitochondria's functions is to help control the concentration of calcium in the cell, which the organelles can rapidly absorb and store. This capacity is important, particularly in instances when calcium levels in the cell spike during a stroke, a condition which contributes a cascading series of events that ultimately lead to a state called excitotoxicity and cell death.
One of the keys to identifying the function of HUMMR has been the appreciation in that the body operates at a relatively low oxygen level. While the air we breath consists of approximately 20% oxygen, the cells in the brain sit at somewhere between 2-5% oxygen. This creates a "normal" state of hypoxia in the brain.
However, the concentration of oxygen in the brain can drop even further in instances such as a stroke, when blood flow to a portion of the brain is cut off. This decrease in oxygen promotes the expression of HUMMR which, in turn, mobilizes mitochondria. More mitochondria in the correct position may mean the cell has a greater capacity to filter out toxic levels of calcium. Rempe and his colleagues are now investigating the role that HUMMR may play in stroke models, particularly whether or not this activity helps protect vulnerable cells that lie just outside the core areas of the brain that are damaged by stroke.
"Ultimately, these advances in our understanding of the molecular and cell biology of mitochondria have the potential to lead to novel approaches for the prevention and treatment of neurological disorders," said Rempe.
Co-authors include URMC researchers Li Yan, MS, and David Hoffman, D.M.D., Howard Federoff, M.D., Ph.D., and Seung Lim, Ph.D. with Georgetown University, and Pontus Aspenstrom, Ph.D. with the Karolinska Institute in Stockholm, Sweden. The study was funded, in part, by the National Institute of Neurological Disorders and Stroke.
Mark Michaud | EurekAlert!
Progress in Super-Resolution Microscopy
17.12.2018 | Julius-Maximilians-Universität Würzburg
Communication between neural networks
17.12.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
Researchers from the University of Basel have reported a new method that allows the physical state of just a few atoms or molecules within a network to be controlled. It is based on the spontaneous self-organization of molecules into extensive networks with pores about one nanometer in size. In the journal ‘small’, the physicists reported on their investigations, which could be of particular importance for the development of new storage devices.
Around the world, researchers are attempting to shrink data storage devices to achieve as large a storage capacity in as small a space as possible. In almost...
The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.
Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...
What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
17.12.2018 | Studies and Analyses
17.12.2018 | Life Sciences
17.12.2018 | Power and Electrical Engineering