Prolonging Life: Disable Mitochondrial Translational Control proteins

How Mitochondria Control Aging
Kirill Stasevich, Compulenta

Mitochondria affect the aging process not only through oxidative stress, the source and liquidator of which it is. Suppression of the activity of proteins serving synthesis in mitochondria leads to an increase in cell life, regardless of its sensitivity to oxidative stress.

Mitochondria of intestinal epithelial cells.
Oxidative reactions of cellular respiration take place on the inner folds of the membrane.
(Photo by professors P. Motta & T. Naguro.)

Mitochondria have long been suspected of involvement in aging processes. These cellular organelles provide the cell with energy, literally burning a variety of fuels inside themselves: nutrients are oxidized in the mitochondria with oxygen, and after a series of biochemical reactions, a high-energy ATP molecule is obtained, which the cell can use for its own purposes. Well, since oxygen is involved in the extraction of energy, along the way there is an accumulation of harmful by–products - free radicals. They are quite aggressive and can disrupt chemical bonds in a variety of biomolecules, including proteins and DNA.

Mitochondria have the tools to quench these dangerous oxidants, but over time there are more radicals, and the cell's defense systems stop coping with them. Oxidative stress is getting out of control. That's how it turns out that mitochondrial power plants, due to the harmfulness of the profession, play a rather serious role in the decrepitude of the cell and the body.

Scientists from the University of Gothenburg (Sweden) have found that turning off some mitochondrial proteins slows down the aging process. It seems to be nothing surprising, but these proteins, as it turned out, have nothing to do with energy and oxidative processes. We are talking about proteins of the internal economy, called mitochondrial translational control proteins (MTS – mitochondrial translational control) and necessary for normal biosynthesis in these organelles. (Mitochondria, by the way, are also remarkable in that they have their own genome, independent of the rest of the cell, and their own protein-synthesizing apparatus; in this sense, mitochondria represent something like a state within a state.)

But these MTS proteins, as it turned out, have powers that go beyond the mitochondria: they affect the stability of the cell genome, chromatin packaging, and the cell's ability to get rid of damaged and dangerous proteins. Mitochondrial proteins have found themselves in close cooperation with some of the signaling molecules of the cell that control the activity of other proteins responsible for the state of chromosomes and the cleaning of protein "garbage" – spoiled and damaged molecules. The researchers experimentally suppressed the synthesis of a number of proteins from the MTS group, and as a result, they observed the "falling asleep" of a significant part of the cellular genome (DNA in chromosomes was tightly packed and closed from reading), an increase in the life of cellular proteins and activation of "cleaning systems"; the cell seemed to slow down its working speed and began to take better care of itself.

Bottom line: with the MTS proteins turned off, the cells lived longer. And more importantly, the prolongation of life in this way was not affected by the sensitivity of cells to free radicals. Thus, yeast cells with MTS proteins turned off maintained viability for the same long time even when they artificially spoiled the enzymes responsible for combating oxidative stress.

The full results of studies on the role of mitochondria in aging are published in the journal Molecular Cell (Caballero et al., Absence of Mitochondrial Translation Control Proteins Extends Life Span by Activating Sirtuin-Dependent Silencing).

From a highly specialized point of view, the experiments of Swedish scientists explain several strange facts that have already been observed – when disturbances in the functioning of mitochondria led to an increase in life in fungi, fruit flies and roundworms. It was believed that any errors in the work of these organelles only lead to an increase in uncontrolled oxidative processes and, consequently, to an acceleration of aging. Now we can say with confidence that all kinds of antioxidants are not rejuvenating apples, not a panacea for death: the same mitochondria affect aging bypassing oxidative processes.

However, the researchers themselves intend to make mitochondrial proteins work to prolong life: since they affect the stability of biomolecules in the cell, is it possible with their help to prevent the development of diseases such as cancer or Alzheimer's disease, which are just related to the looseness of the genome and disorders in the synthesis and packaging of proteins?..

Prepared based on the materials of PhysOrg: The body's power stations can affect aging.

Portal "Eternal youth" http://vechnayamolodost.ru11.05.2011