Spotlight on Mitochondria

Throughout my graduate and postgraduate studies I have been really intrigued and fascinated by the mitochondria, the organelle that keeps all of us running everyday! The more I learn about them, the more intricate they get.

Historical Perspective on Mitochondria Function

Traditionally, mitochondria were known to be a static organelle that is involved in energy production, earning the nickname “powerhouse of the cell”. But, in recent years we have learned that mitochondria are extremely dynamic organelles and can change their shape and structure by undergoing fusion and fission events to cope with metabolic demands.

Mitochondrial respiratory chain complexes generate energy for the cells by shuttling electrons and ultimately consuming oxygen to produce ATP (energy currency of a cell). Mitochondria are also a site of reactive oxygen species (ROS) production, which results from electrons escaping through mitochondrial respiratory chain. The efficiency of mitochondria to produce more ATP while reducing ROS production may be crucial for cell survival in various disease conditions.

Mitochondrial Supercomplexes

This brings us to the exciting findings in the last few years uncovering mitochondrial machinery called supercomplexes that help mitochondria to achieve this goal. Supercomplexes are mitochondrial respiratory chain complexes that form a mega-complex by assembling together as one unit; this minimizes distance travelled by electrons shuttling between complexes and makes it more efficient.

Another exciting development in the field of mitochondrial biology is the discovery that ATP synthase (site of ATP production) also acts as the mitochondrial permeability transition pore. It has been long known that under pathological conditions such as stroke there is an opening of a conductance channel within the mitochondrial inner membrane causing ionic and osmotic imbalance, depolarization, and ultimately leading to cessation of ATP production. However, the molecular identity of this pore has been a mystery for long time. Lately, mitochondrial ATP synthase has attracted a considerable attention as a potential pore forming machinery. Several studies have elegantly shown that ATP synthase is indeed the core component of permeability transition pore (PTP). However, the exact component of the ATP synthase that constitutes the pore is still intensely debated. There are several models put forward by which ATP can form PTP 1) ATP synthase assembles as dimers and forms a pore between them; 2) C-ring confirmation induces pore and 3) Beta subunit of ATP synthase can be directly activated by calcium ions to induce pore opening.

Mitochondria and Stroke

Mitochondria are indispensible to neurons because these high-energy demanding cells depend entirely on mitochondrial ATP production for their energy. This energy production is of paramount importance to neuronal survival and function, as failure to generate sufficient ATP is implicated in neuronal death in pathological conditions such as stroke. Stroke is one of the most debilitating conditions to live with, and also more prevalent in elderly population. Given that our lifespan is getting longer, using these strategies to manipulate mitochondria in our favor represents a huge therapeutic potential.