Field of Science

Mitochondrial Networks

ResearchBlogging.orgHaving taken a brief look at some plastids last week, I thought I should probably balance things out by writing about mitochondria; the energy generating centres of the (eukaryote) cell. Like plastids, mitochondria are thought to originate from endosymbiosed bacteria-like organisms and are often shown as looking something like the picture on the right. As well as creating energy in the form of ATP mitochondria are also involved in the B-oxidation of fatty acids (producing energy from fats), Iron-sulfur cluster generation, oxygen metabolism, cell death control and Calcium ion buffering and signalling.

Mitochondria are surrounded by two membranes, an inner (the Inner Mitochondria Membrane - IMM) and an outer (OMM). The inner membrane is the main barrier to the outside world and contains most of the energy-making apparatus either embedded in it or present in the inter-membrane space. The outer membrane is used to coordinate function with signalling, and plays a part in apoptosis, or organised cell death.

In the cell however, mitochondria are often not found in the neat little packages as shown above, but instead fuse together to form long cell-wide tubular arrangements. Usually, they can be found in both vesicle and tube like states, constantly fusing or breaking up depending on cell circumstances, the type of cell, or the functional state of the mitochondria. The result is shown below; a network of mitochondria within the cell:Two processes are involved in the creation and maintenance of this tubular network. Fusion; the joining of mitochondria, and fission; where they split apart.

Fusion: mitochondrial fusion is controlled by large GTP proteins, which use the hydrolysis of GTP to produce energy to join the two membranes together. OMM localised proteins Mfn1 and 2 carry out the initial tethering and joining of the OMM by forming coiled-coil type interactions of their C-terminals which acts to bring two mitochondria together. Once the outer membranes have fused, OPA1 (a soluble protein found in the inter-membrane space) fuses together to join the inner membranes. The fusion of both the outer and inner membrane is usually highly synchronous, although studies in yeast have shown the two fusions can be decoupled.

Fission: in contrast, fission is controlled not by GTPases, but by a protein related to dynamin called Drp1. Drp1 is usually found in the cytosol, but it can localise to the mitochondria in clumps which lead to active fission sites. The Drp1 forms polymers which wrap spirally around the mitochondrial tubule and lead to it splitting. It is thought to be recruited to specific sites by the mitochondrial-bound protein Fis1, although this still requires further study.

As aberrations in mitochondria dynamics are generally associated with neurodegenerative disorders, the control and organisation of these processes are vital. A variety of cofactors and inhibitors have been found that can regulate the Mfn proteins involved in fusion, and OPA1 is thought to be controlled by alternative proteolysis to create different isoforms. There are a number of different protein kinases that are able to phosphorylate the Drp1 fission protein, which not only allows a large degree of control, but means that this control can be synchronised with different intracellular signaling pathways, giving more integrated cellular control.

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Benard G, & Karbowski M (2009). Mitochondrial fusion and division: Regulation and role in cell viability. Seminars in cell & developmental biology, 20 (3), 365-74 PMID: 19530306

3 comments:

becky said...

I was recently in a general cell biology course and my professor happened to mention that the common thought of mitochondria being endocytosed by a bacteria couldn't have happened because the ability of bacteria to endocytose objects occurred after the mitochondria appeared in the cell. I just want to know what your take on this is. Is there any evidence either way?

Lab Rat said...

I think at the moment the majority of evidence points towards endosymbiosis. I'd never heard of phagocytosis (the engulfing procedure) evolving later, and given that most bacteria nowadays (which don't have mitochondria) can phagocytose no problem I think I'd support that. I'm not saying your Professor is wrong, just that his statement is extremely unlikely.

I'd be very interested to know what evidence he cites for that view. I'm guessing actin development might have something to do with it?

(btw, I am just about to go on holiday, so might not be able to get back to this until January)

Anonymous said...

Is there any evidence from other technique such as EM for this kind of mitochondrial network? My curious is whether the confocal microscopy provides resolution high enough to distinguish individual mitochondria which are close to each other?