Tuesday, 20 March 2012

Taking the pulse of cellular power stations

Discharge and recharge: why cellular power stations might pulse 

An abstract representation (acrylic on canvas) of a single
mitochondrion undergoing a 'pulse'. Its change in energy status
is shown by the change in colour that we have also observed by
microscopy using fluorescent sensors. Artist: Markus S
We've just written an article in the journal Plant Cell about pulsing cellular power-stations and will motivate it by an analogy. Imagine we have a reservoir of water, and this water flows downhill through an outlet pipe, turning a turbine and producing energy. In this thought experiment, we're faced with a problem: the only way we can get water into our reservoir is by pumping it into the bottom of the reservoir. The higher up a reservoir is, the harder it is to pump water up there and the higher the risk of pumps overheating and getting damaged. 


The problem can be solved by allowing the height of our reservoir to vary. If we lower our reservoir, it will become easier to fill, and the higher water pressure that arises from an increasingly filled reservoir will partly compensate for the fact that turbine-turning water will flow downhill from a lowered height, while allowing the pumps to relax and cool.

This model is a crude representation of mitochondria, the power stations of the cell, which use energy from respiration to create an energetic gradient across their membranes -- like a natural version of an AA battery. In our picture, this corresponds to the pumps feeding into our reservoir -- and in the cell, these pumps produce dangerous chemicals when they are overworked. The gradient they produce imbues protons with energy that is part electrical -- which we picture as the height of our reservoir -- and part chemical -- which we picture as the amount of water in our reservoir. These protons then flow through a protein complex -- the turbine -- to produce ATP, the universal cellular fuel.

When mitochondria pump many protons, their "reservoirs" rise, with the increase in height forcing the pumps to work harder to pump water into the reservoir. This work produces dangerous chemicals which can damage the cell and the mitochondria themselves (called reactive oxygen species - they're what antioxidants try to combat). We have found a new mechanism by which this risk is decreased: if mitochondria are having to work hard, they "pulse", spontaneously lowering the height of their reservoir. This decreases the amount of work that the mitochondrial pumps have to do to fill the reservoir. The amount of turbine-turning energy per unit of water decreases, but as it becomes easier to fill the reservoir, more water gets pumped into it, partly compensating for the loss of height by an increase in volume. The pulsing process thus lowers the reservoir but fills it with more water, allowing the mitochondrial pumps to relax and reducing the production of dangerous chemicals.



We observed these pulses, spontaneous decreases of mitochondrial membrane potential, in Arabidopsis thaliana, a model plant species used in many biological contexts. Treating plant mitochondria with a variety of chemicals and observing the effects on pulsing, we deduced a biochemical mechanism by which pulsing occurs: a controlled influx of cations such as calcium ions into the mitochondrial matrix decreases membrane potential. We also found that pulsing is increased when plants face stressful environments: if they are suddenly heated, for example, or exposed to toxic chemicals. This novel mechanism may help explain some of the variability that our cellular engines exhibit and may be an important discovery in considering how mitochondria react to dangerous cellular conditions. You'll find the article free by following this link.  This article about single mitochondria complements our work on the mitochondrial population of the cell - we blogged about that here and here. Iain, Markus & Nick.