Mitochondria: Movable Tuners of Signaling in the Cell
Mitochondria are dynamic and versatile organelles with two main well-known tasks of providing energy (ATP) and Calcium (Ca2+) buffering. These essential components can be considered as movable tuners of signaling events that the cell can deploy when they are most needed. In many cell types, what facilitates their movement is a constant process of fission and fusion. A balance between fission and fusion controls not only the overall mitochondrial morphology but also its size and number.
Mitochondrial fission is mediated by Dynamin-related protein (DRP1) which shuttles onto and off mitochondria. At the division sites around the outer mitochondrial membrane these proteins assemble into spirals to drive the fission process. During mitochondrial fission, a tubular organelle named as Endoplasmic Reticulum (ER) is found in contact with mitochondria in the future fission sites to which DRP1 is recruited. Another protein from the Dynamin family named as mitofusin2 (MFN2) was suggested to act as a tether between mitochondria and ER and mediates mitochondrial fusion. Mutations that inhibit mitochondrial fission results in excessively tubular mitochondrial network due to ongoing fusion.
Why Mitochondrial fission-fusion matters?
One simple effect of mitochondrial fission-fusion is related to the mobility of mitochondria; Mitochondrial fission can facilitates mitochondrial mobility simply because smaller particles can move more efficiently. Fusion, instead, promotes tethering to other cellular structures such as ER. Another important aspect of mitochondrial fission is to eliminate the dysfunctional mitochondria; These dynamic organelles contain DNA (mtDNA) and DNA containing harmful mutations can be pathogenic. Fission and Fusion mix mtDNA in different compartments until the pathogenic content becomes so overwhelming.
The positioning and translocation of mitochondria is controlled by a motor-based transport along microtubules (or actin filaments) which guide mitochondrial positioning. These cylindrical structures are comprised of Tubulin dimers. While one end of the molecular motors bind to the sites on microtubules, the other end attaches to the mitochondria. Through walking along microtubules, these molecular motors control the mitochondrial movement and translocation in the cell.
Mitochondrial Dynamics and Immunology
As key bioenergetic organelles mitochondria have to be transported to all the specific high-energy demanding sites within the cell. One of these sites is immunological synapse which is a contact site between activator (Antigen presenting cell, APC) and effector cells. It is formed as the initial response of the immune cell to an external cue. Mitochondrial dynamics are crucial to fuel synaptic transmission. This dynamical effect following a morphological change directly links mitochondria to the antiviral defense of the cell.
Mitochondria accumulate at the immunological synapse to provide energy for immunological synapse formation and maintenance. Mitochondrial translocation to the plasma membrane and immunological synapse is performed via motor protein apparatus as mentioned above. For this relocation, the fission machinery plays an important role; The isolation of single mitochondria from the main network by fission is essential for their transport resulted in the accumulation of fragmented mitochondria at the synapse.
Mitochondrial morphology and dynamic is important in the regulation of multiple cell functionality. So far potential connection between several pathologies and mitochondrial shape and movement has been researched. For instance, impaired mitochondrial function and increased fragmentation of mitochondria was reported in Parkinson’s disease patients, or elongated mitochondria has been shown in Alzheimer’s disease. Especially, the quick change in mitochondrial form in response to cell conditions shows how important it is to acquire a detailed knowledge about the mitochondrial fission/fusion process.
References:
[1] “Diverse Roles of Mitochondria in Immune Responses: Novel Insights Into Immuno-Metabolism”, Anusha Angajala, et al.
[2] “From Structure to Function: Mitochondrial Morphology, Motion and Shaping in Vascular Smooth Muscle”, John G. McCarron, et al.
[3] “Structural insights into oligomerization and mitochondrial remodeling of dynamin 1-like protein”, Chris Fröhlich, et al.
[4] “Mitofusin 2: from functions to disease”, Riccardo Filadi, et al.
Forms & Functions 