24 June 2014

How to get rid of old mitochondria

Some neurons resort to the help of astrocytes

LifeSciencesToday based on UC San Diego (Getting Rid of Old Mitochondria)
and Johns Hopkins Medicine (Neurons Get Their Neighbors To Take Out Their Trash).

It is widely recognized in science that cells themselves destroy and recycle their old or damaged organelles, but recently scientists at the University of California, San Diego School of Medicine, Johns Hopkins University School of Medicine and the Kennedy Krieger Institute have been studying at the University of California, San Diego School of Medicine. Institute) put the correctness of this position into reasonable doubt by demonstrating that some neurons transfer the function of disposing of mitochondria they don't need–tiny intracellular power stations –to glial cells known as astrocytes.

The data confirming their conclusions, published in the early online edition of PNAS (Davis et al., Transcellular degradation of axonal mitochondria), suggest the need to revise some of the fundamentals of biology. But they also have practical significance, deepening the understanding of many neurodegenerative diseases and metabolic disorders and opening the way to improving their treatment methods.

"This casts doubt on the generally accepted postulate that cells necessarily destroy their organelles themselves. We do not yet know how generalized this process is if we consider the brain as a whole, but our work suggests its likely widespread prevalence," says one of the leading co–authors of the study, Mark Ellisman, PhD, Professor Emeritus of neurology, director of the National Research Center for Microscopy and Imaging (National Center for Microscopy and Imaging Research) UC San Diego.

"The discovery of the standard process of garbage transfer from neurons to glia is likely to be very important for understanding the age–related decline in brain function and neurodegenerative or metabolic diseases," comments the study's other lead co-author Nicholas Marsh-Armstrong, PhD, a neurologist from Johns Hopkins University and the Institute Kennedy Krieger. "We expect it to have a significant impact on other areas of biomedicine as well."

Scientists focused their attention on the axons of retinal ganglion cells – neurons that transmit visual information from the eye to the brain. The impetus for this study was the observations made by Dr. Marsh-Armstrong during the study of a mouse model of glaucoma, that protein products from the retina accumulate in the optic nerve head directly behind the eye.

Reconstruction of electron microscopy data showing a part of the retinal ganglion cell (blue) in the optic nerve head of a normal healthy mouse. Its two bulges are filled with mitochondria (red). Scientists believe that this is one of the stages of the process of removing mitochondria for their further destruction by neighboring astrocytes. (Photo: Keun-Young Kim/PNAS)Using advanced microscopy techniques and molecular techniques developed in the laboratories of Ellisman and Marsh-Armstrong, the researchers found that the damaged mitochondria of retinal ganglion cells are collected at the head of the optic nerve – where the axons of ganglion cells exit the eye, forming the optic nerve going to the brain.

These mitochondria are absorbed and destroyed by neighboring astrocytes – the most common glial cells of the vertebrate nervous system and the only cells connecting brain neurons with blood.

The optic nerve and retina of the mouse, responsible for transmitting information from the eye to the brain. The tissue is stained with fluorescent substances showing the distribution of astrocytes (yellow), axons of retinal ganglion cells (purple), myelin (green) and cell nuclei (blue). Axons of retinal ganglion cells transmit mitochondria to nearby astrocytes in the optic nerve head behind the retina. Astrocytes destroy these mitochondria in a process called transmitophagy. (Photo: Mark Ellisman, NCMIR, UC San Diego)This discovery refutes the generally accepted axiom that all cells themselves isolate, destroy and remove damaged molecules and organelles – a process known as autophagy (translated from Greek "self-eating").

If mitochondria are involved in this process, it is called mitophagy. The process described by Marsh-Armstrong, Ellisman and their colleagues is called transmitophagy.

However, many questions related to this amazing discovery remain unanswered. For example, do mitochondria moving to the head of the optic nerve originate only from a population located in long conductive nerve fibers running from the eye to the brain, or are some mitochondria actively transported from the retina itself?

According to Dr. Ellisman, the results of this study will deepen the understanding – and, perhaps, eventually, improve the treatment – of a number of diseases.

"Mitochondria play an important role in the health of axons, which are absolutely necessary for the interaction of neurons and the transmission of information. Further study of what happens in the process of transmitophagy and whether violations in this phenomenon contribute to the development of neuronal dysfunctions or diseases should become a priority area of research," the scientist believes.

The significance of the results of this study goes far beyond the optic nerve, as the accumulation of "garbage" inside cells causes neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis, says Dr. Marsh-Armstrong. "By showing the existence of this alternative type of recycling, we have opened the way for others to study whether similar processes can occur with other types of cells or with cellular components other than mitochondria."

Portal "Eternal youth" http://vechnayamolodost.ru24.06.2014

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