Dr. Luis Beltran-Parrazal
My main research interest is to understand the biophysics of mitochondria in the brain at both the cellular and organism levels. I have been studying the signaling pathways that induce mitochondrial movement in neurons and the functional properties and regional distribution of mitochondria in different metabolic states, e.g., those induced by excitability and inhibitory electrical activity in neurons. Mitochondria are critical components of eukaryotic cellular metabolism. This is particularly true in the case of neurons, which in their morphology and functions are among the most complex and specialized of all animal cells. Moreover, the brain is a metabolically expensive organ, accounting for as much as 20% of an animal’s day-to-day energy consumption. Most of the brain’s energy requirements are met through aerobic respiration, specifically through mitochondrial production of adenosine triphosphate, or ATP, yet we still do not fully understand the relationship between mitochondria and neuronal function in the context of specific brain states. Moreover, impairment of mitochondrial function has been implicated in a number of brain pathologies, including Alzheimer’s, Parkinson’s diseases, and amyotrophic lateral sclerosis.
Using high temporal and spatial resolution confocal microscopy imaging I have described in cortical neurons the movement of mitochondria and changes in intracellular [Ca2+]I simultaneously in dendrites and axons. I have described quantitatively the velocity, direction, and pattern of mitochondrial movement and shown that these parameters are not affected by transient increases in [Ca2+]i associated with spontaneous firing of action potentials. Moreover, I have demonstrated that the stimulation of [Ca2+]i transients with forskolin, or bicuculline, or sustained elevations of [Ca2+]i evoked by glutamate have no effect on mitochondrial trafficking in neurons. My results show that movement of mitochondria along processes is a fundamental activity in neurons and occurs independently of physiological changes in [Ca2+]i associated with action potential firing, synaptic activity, or release of [Ca2+]i from intracellular stores. These observations have changed our way of thinking about how Ca2+ modulates the distribution of mitochondria in neurons.
My main research interest is to determinate the molecular mechanisms that allows mitochondrial movement and distribution throughout the neurons, and how mitochondria modify the homeostasis of intracellular Ca2+ and electrical activity. I am also interested in pursuing some other exciting projects such as exploring the role of mitochondria as sink of Ca2+ in neurons and glia, and how the signal pathways activated by neurotrophic factors such as EGF modulate the flux of Ca2+ between the cytosol and mitochondrial matrix. Answering these questions not only add to our understanding of the biophysics and molecular biology of mitochondria but also may have relevance directly related with normal and pathological state of the brain.
Concurrently with my mitochondria project I have been studying how Ca2+ in neurons and glia modulates the rhythmic release of neuropeptides, K+ channels conductance, and the transcriptom. Ihave been using techniques such as whole cell patch in current- and voltage-clamp modes, confocal Ca2+ imaging, and real time PCR combined with the use of transgenic mouse, viral transfection, and pharmacology, all of these to understand the participation of Ca 2+ in normal and pathophysiological neuronal and glia states.
During my postdoctoral training I have had the opportunity of learning the basic principles of home-made and custom-made technology. I have learned the basic construction and modification of confocal and fluorescent microscopes. I program in ImageJ, Labview, and Mathlab to automatized the acquisition, quantification and analysis of my data. My goal is to have the opportunity to transfer my knowledge and experience to future trainees showing that it is possible to built cutting edge optic, mechanic, and electronic devices to answer basic and clinical questions even when budget is limited.
I believe my research and technical knowledge will lead to a better understanding of the role of mitochondrial dynamics in the onset of neurological disease, as well as help to gain insights into the relationship between mitochondria and normal brain function. The long-term goal of my research is to ensure their relevance and applicability.