What happens in the mitochondrion?
The mitochondrion is the powerhouse of the cell. In humans, its proteome is composed of approximately 1000 proteins, only 13 of which are produced by mitochondrial DNA. The remainder come from nuclear DNA.
A first scientific issue is understanding signaling from mitochondria to nuclear DNA; here we need to uncover more and more proteins involved in signaling, their reciprocal interactions, and interactions with nuclear and mitochondrial DNA.
A second challenge regards the import of proteins and their trapping in the mitochondrial intermembrane space (IMS) and matrix. Here the research is active and progress is continuous.
Finally, metal ions have to reach the mitochondrion: the biogenesis of all iron-sulfur proteins occurs in the matrix, and then they must translocate; the assembly of cytochrome c oxidase with copper and iron metals occurs in the IMS. This is just to mention two major biological processes whose perfect function is necessary for a healthy status. Understanding the traffic and homeostasis of metal ions is another challenge.
Of course a goal of Instruct is that of providing instrumentation and expertise to address fundamental questions such as: i) understanding processes, in a systems biology frame, with interactions characterized by atomic resolution 3D structures of the various actors; ii) evaluating quantities of proteins in the various cellular organelles; iii) determining thermodynamic and kinetic parameters; iv) understanding the origin of diseases from the genetic and then structural points of view including the aberrant polymerization of proteins such as SOD1 in the IMS.
All the techniques typical of Instruct are needed for this challenge: protein expression and labeling, crystallography and NMR for structure determination, NMR for weak and transient interactions, NMR for the characterization of proteins in cell and in organelles, mass spectrometry for proteomics and the detection of interactions, electron microscopy to observe aggregates and large systems, in cell molecular biology, and all the biophysical techniques for biomolecular characterization.
The final goal is understanding the interrelations between mitochondria and the whole cell.