Mitochondrial protein biogenesis in mammalian cells
How proteins are trafficked through the confines of the cell and integrated into the appropriate cellular compartments has puzzled and intrigued researchers for decades. Most mitochondrial proteins are nuclear-encoded, synthesised in the cytosol as immature precursors and are subsequently targeted and imported into the organelle. In human mitochondria ∼1500 nuclear-encoded proteins must reach the organelle following synthesis in the cytosol. This giant task relies on sophisticated protein import pathways that are executed by dynamic molecular machines, known as “translocases” (Figure 1).
Figure 1: Mitochondrial Transport Machineries. The greater part of all mitochondrial proteins are encoded by nuclear genes and synthesised as precursor proteins on cytosolic ribosomes. The immature proteins must be targeted to and imported into mitochondria. The translocase of the outer mitochondrial membrane (TOM complex) is the main entry gate into mitochondria. Upon outer membrane translocation different sorting pathways are initiated depending on the targeting elements contained within the precursor. Shown here are the translocation machineries that aid in this process.
The biological problem: We have limited understanding of the machineries and mechanisms that govern mitochondrial protein import in human cells since this has classically been investigated using fungal cell models. However, higher eukaryotic cell models provide an exciting platform to investigate the broader implications of mitochondrial protein import on cell physiology, and how disturbances in these pathways influences mitochondrial function and cell health.
Our work aims to identify the protein components and mechanisms that contribute to protein import in mammalian cells. We aim to provide novel descriptions regarding cellular protein trafficking in eukaryotic cells and contribute to understanding the molecular basis of mitochondrial dysfunction and disease.
Dr Stojanovski embraces a large range of technologies from protein chemistry to molecular cell biology and she is passionate about teaching these methods and the knowledge of her discipline to younger scientists. The described projects use a wide range of experimental approaches, including:
- mammalian tissue culture
- bacterial expression systems
- recombinant protein technologies
- cellular imaging techniques
- Blue-native PAGE
- affinity techniques and proteomics
- yeast culturing and genetics
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