Mitochondria how many membranes

For instance, releasing calcium back into a cell can initiate the release of a neurotransmitter from a nerve cell or hormones from endocrine cells. Calcium is also necessary for muscle function, fertilization, and blood clotting, among other things. Because calcium is so critical, the cell regulates it tightly. Mitochondria play a part in this by quickly absorbing calcium ions and holding them until they are needed. Other roles for calcium in the cell include regulating cellular metabolism, steroid synthesis , and hormone signaling.

When we are cold, we shiver to keep warm. But the body can also generate heat in other ways, one of which is by using a tissue called brown fat. During a process called proton leak , mitochondria can generate heat. This is known as non-shivering thermogenesis.

Brown fat is found at its highest levels in babies, when we are more susceptible to cold, and slowly levels reduce as we age. However, the majority of mitochondrial diseases are due to mutations in nuclear DNA that affect products that end up in the mitochondria. These mutations can either be inherited or spontaneous. When mitochondria stop functioning, the cell they are in is starved of energy.

So, depending on the type of cell, symptoms can vary widely. As a general rule, cells that need the largest amounts of energy, such as heart muscle cells and nerves, are affected the most by faulty mitochondria. Diseases that generate different symptoms but are due to the same mutation are referred to as genocopies. Conversely, diseases that have the same symptoms but are caused by mutations in different genes are called phenocopies.

An example of a phenocopy is Leigh syndrome , which can be caused by several different mutations. Over recent years , researchers have investigated a link between mitochondria dysfunction and aging. There are a number of theories surrounding aging, and the mitochondrial free radical theory of aging has become popular over the last decade or so.

The theory is that reactive oxygen species ROS are produced in mitochondria, as a byproduct of energy production. These highly charged particles damage DNA, fats, and proteins.

Because of the damage caused by ROS, the functional parts of mitochondria are damaged. When the mitochondria can no longer function so well, more ROS are produced, worsening the damage further. Although correlations between mitochondrial activity and aging have been found, not all scientists have reached the same conclusions.

Their exact role in the aging process is still unknown. Mitochondria are, quite possibly, the best-known organelle. Mitochondria are membrane-bound organelles, but they're membrane-bound with two different membranes. And that's quite unusual for an intercellular organelle.

Those membranes function in the purpose of mitochondria, which is essentially to produce energy. That energy is produced by having chemicals within the cell go through pathways, in other words, be converted. Figure 2: The electrochemical proton gradient and ATP synthase At the inner mitochondrial membrane, a high energy electron is passed along an electron transport chain. The energy released pumps hydrogen out of the matrix space. The gradient created by this drives hydrogen back through the membrane, through ATP synthase.

At the end of the electron transport chain, the two electrons are used for the conversion of oxygen O 2 to water H 2 O. The build up of transported protons in the intermembrane space causes a gradient that is used by ATP synthase to produce ATP.

ATP synthase is depicted as a vase-shaped protein that spans the inner membrane. A piece of the inner and outer mitochondrial membranes is shown.

The membranes are depicted as lipid bilayers. The lipids have pink, circular heads and purple tails and are arranged in two rows with their heads facing outward and their tails facing each other. The outer membrane is shown along the top and side perimeter of the diagram. The inner membrane lies interior to the outer membrane. The space between the two membranes is the intermembrane space, and the space within the inner membrane is the matrix.

Three boxy shapes embedded in the inner membrane — shown in orange, green and pink from left to right — represent the proteins of the electron transport chain. Two electrons are represented by a small, blue sphere, which is labeled 'e -.

Mitochondrial genomes are very small and show a great deal of variation as a result of divergent evolution. Mitochondrial genes that have been conserved across evolution include rRNA genes, tRNA genes, and a small number of genes that encode proteins involved in electron transport and ATP synthesis. The mitochondrial genome retains similarity to its prokaryotic ancestor, as does some of the machinery mitochondria use to synthesize proteins.

In addition, some of the codons that mitochondria use to specify amino acids differ from the standard eukaryotic codons. Still, the vast majority of mitochondrial proteins are synthesized from nuclear genes and transported into the mitochondria. These include the enzymes required for the citric acid cycle, the proteins involved in DNA replication and transcription, and ribosomal proteins.

The protein complexes of the respiratory chain are a mixture of proteins encoded by mitochondrial genes and proteins encoded by nuclear genes. Proteins in both the outer and inner mitochondrial membranes help transport newly synthesized, unfolded proteins from the cytoplasm into the matrix, where folding ensues Figure 3.

Figure 3: Protein import into a mitochondrion A signal sequence at the tip of a protein blue recognizes a receptor protein pink on the outer mitochondrial membrane and sticks to it. This causes diffusion of the tethered protein and its receptor through the membrane to a contact site, where translocator proteins line up green.

In ageing mitochondria, the cristae recede into the boundary membrane, with ATP synthases dimer rows along the shallow inner membrane ridges. Outer membrane, transparent grey ; inner membrane, light blue.

ATP synthase F 1 heads are shown as yellow spheres. Right : subtomogram averages with fitted X-ray models. Red lines , convex membrane curvature as seen from the matrix ; blue lines , concave membrane curvature. Adapted from [ 56 ]. The observed morphological changes during ageing in P. The electron-transfer reactions in complexes I and III generate reactive superoxide radicals as side products [ 58 ], which cause damage to mitochondrial proteins and DNA, as well as to other cellular components.

Senescent mitochondria that lack cristae and ATP synthase dimers would not be able to provide sufficient ATP to maintain essential cellular functions. Cells normally deal with oxidative damage by oxygen radical scavenging enzymes such as superoxide dismutase or catalase, as well as by mitochondrial fission and fusion.

Damaged or dysfunctional mitochondria are either complemented with an undamaged part of the mitochondrial network by fusion or sorted out for mitophagy [ 59 ]. During ageing, fission overpowers fusion and the mitochondrial network fragments [ 60 ]. This prevents the complementation of damaged mitochondria by fusion and thus accelerates their deterioration. Even though mitochondria and their membrane protein complexes have been studied intensely for more than five decades, they remain a constant source of fascinating and unexpected new insights.

Open questions abound, many of them of a fundamental nature and of direct relevance to human health [ 61 ]. Concerning macromolecular structure and function, we do not yet understand the precise role of the highly conserved feature of ATP synthase dimers and dimer rows in the cristae and the interplay between the MICOS complex and the dimer rows in cristae formation.

Are there other factors involved in determining crista size and shape? We still do not know how complex I works, especially how electron transfer is coupled to proton translocation.

What is the role of respiratory chain supercomplexes? Do they help to prevent oxidative damage to mitochondria, and if so, how? And how does this affect ageing and senescence? How does it anchor the cristae to the outer membrane, and how does it separate the cristae form the contiguous boundary membrane? Similarly, the mechanisms of mitochondrial fission and fusion and the precise involvement and coordination of the various protein complexes in this intricate process is a fascinating area of discovery.

The biogenesis and assembly of large membrane protein complexes in mitochondria is largely unexplored. Where and exactly how do the respiratory chain complexes and the ATP synthase assemble?

How is their assembly from mitochondrial and nuclear gene products coordinated? Does this involve feedback from the mitochondrion to the cytoplasm or the nucleus, and what is it? And finally, how exactly are mitochondria implicated in ageing? Why do some cells and organisms live only for days, while others have lifespans of years or decades?

Is this genetically programmed or simply a consequence of different levels of oxidative damage? How is this damage prevented or controlled, and how does it affect the function of mitochondrial complexes?

Is the breakdown of ATP synthase dimers also an effect of oxidative damage, and is it a cause of ageing? It will be challenging to find answers to these questions because many of the protein complexes involved are sparse, fragile and dynamic, and they do not lend themselves easily to well established methods, such as protein crystallography. Cryo-EM, which is currently undergoing rapid development in terms of high-resolution detail, will have a major impact but is limited to molecules above about kDa [ 62 ].

Even better, more sensitive electron detectors than the ones that have precipitated the recent resolution revolution, in combination with innovative image processing software, will yield more structures at higher resolution. However, small, rare and dynamic complexes will remain difficult to deal with.

New labeling strategies in combination with other biophysical and genetic techniques are needed. Cloneable labels for electron microscopy, equivalent to green fluorescent protein in fluorescence microscopy, would be a great help; first steps in this direction look promising [ 26 ]. Once the structures and locations of the participating complexes have been determined, molecular dynamics simulations, which can analyze increasingly large systems, can help to understand their molecular mechanisms.

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