Cholesterol, the noble fat’s self-sacrificial role in intracellular ecology....
or ...what is the point(s) of the outer mitochondrial membrane?
The mitochondrial outer membrane was, not so long ago, regarded as a vestigial relatively simple ‘candy-wrapper’ for the immensely folded, complex protein rich inner membrane which did all the heavy lifting for the complete oxidation of foodstuffs. The respiratory chain resides on the inner membrane and the chemiosmotic synthesis of ATP is now the hated stuff of undergraduate biochemistry.
Today though, the outer membrane which resembles the other bounding membranes in the cell, is seen to have a literally a life or death role in the cell. The death of a cell is brought about swiftly when the outer membrane becomes permeable to Cytochrome C which itself is only lightly bound to the inner membrane. By the way, I showed forty years ago that in mitochondria from senescent rats Cytochrome C is even more easily detached. So, woe betide a cell that is senescent, cancerous or virus-ridden if the outer membrane ‘decides’ to leak and so trigger cell death.
The point above is that it illustrates that our symbiotic energy-producing ‘guest’ organelle the mitochondria has more in common with a ‘Chernobylesque’ nuclear power pack than it does with AAA batteries in terms of ‘risk to health’ versus energy benefits.
Along the lines of risk, mitochondria are the principle, if accidental, generators of so-called ROS species, free radicals that will oxidise (viz destroy) anything in their path. Dealing with free-radicals is naturally a major preoccupation of the cell and there are many signalling pathways to integrate with the valiant and lightning fast efforts of catalase and superoxide dismutase enzymes which mop up reactive species that escape to the cytoplasm. Mitochondria are high maintenance.
Now, if you had a ‘nuclear reactor’ in your house, you would take care to keep it in a box that a) did not leak its chemicals and b) mostly stopped radiation from getting out. So I was looking for what it is about the outer mitochondrial membrane that acts as a radiation shield, or more accurately a free-radical shield.
Mitochondria generate singlet oxygen, a very dangerous oxidising agent, but which singlet oxygen is short lived and travels only a short distance. Chemists exploit the electronic structure of our old friend cholesterol especially to trap singlet oxygen because it is so good at it. I think this utility of cholesterol is in play in a biological context too.
My hypothesis is that the presence of cholesterol in the outer membrane, (which can be quite high and reflects dietary cholesterol levels), is less to do with regulation of membrane fluidity and permeability but is more part of shielding the ‘reactor’ against singlet oxygen emission. Cholesterol, by the way, assiduously traps singlet oxygen far better than the phospholipids’ double bonds in the membrane bilayer.
Cholesterol itself is oxidised by singlet oxygen and undergoes some complex free radical chemistry before it terminates the chain reaction. Its oxidised products migrate from the membrane quickly to be replaced with fresh cholesterol.
The cholesterol as a shield idea is just a hunch, but it is consistent with an emerging picture of the mitochondrion’s outer membrane. A membrane on a journey from a ’candy wrapper’ to something that has an important role in keeping ‘everyone’ in the intra-cell ecosystem safe from this valuable but lethal guest.
Post Script:
I confess to having in my mind a picture of the mitochondrion as ex-free living prokaryotes shorn of their tough outer coats and re-wrapped in the outer-membrane in the form as shown in every text book
I am not so sure now. Am I simply making an assumption, not unreasonably, from the appearance of mitochondria obtained in isolates and as shown on conventional transmission electron micrographs that this is how mitochondria are actually in vivo.?
The outer-membrane is almost continuous with smooth ER and its lipid composition reflects this intimately. Mitochondria themselves are well known to fuse and split continually, forming every shape from tube-like structures sometimes extended into reticulate arrangements to small, almost spherical, units which can zoom through the cytoskeleton streams to all parts of the cell.
Sometimes the conventional mitochondrial model is obvious, especially when mitochondria are parcelled up for the muscle sarcoplasm or stacked to power the motors in spermatozooa.
When mitochondria are 'parcelled up' it is when they are required to produce maximum yields of energy in short bursts. When they are in their least recognisable forms they are tubular and reticulate. In this case, as in cell division they are required to produce large amounts of energy of a long period of time.
I wonder in terms of the shield article above whether the morphology is important. High energy equals high shield needs.
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