The role of autophagy in mitochondrial protein translation initiation

2017-02-24T02:00:05Z (GMT) by May, Alexander Ian
Autophagy, which was originally identified in yeast, is a fundamental catabolic pathway that facilitates the isolation and transport of cytoplasmic material to the vacuole for degradation. Products of this degradation can then be returned to the cytosol for subsequent biosynthesis. Although autophagy is highly conserved throughout virtually all eukaryotes and the core mechanism of this pathway is well characterised, the physiological significance of autophagy remains poorly understood. As yeast often face conditions of nutrient limitation, it is generally assumed that autophagy acts as a recycling mechanism, supplying anabolic pathways during unfavourable environmental conditions, but limited evidence supports this notion. In this thesis, the physiological role of autophagy in Saccharomyces cerevisiae is discussed with a particular focus on the growth phenotypes of strains defective for autophagy. It is demonstrated that autophagy mutant strains on media supplemented with respiratory carbon sources experience a prolonged lag phase of growth. This phenotype is limited to strains lacking core components of the autophagy machinery and not selective forms of autophagy, such as mitophagy. Further interrogation of this phenotype revealed that autophagy most likely plays a role in the provision of one-carbon metabolites to the mitochondrion, supporting mitochondrial protein translation. These results suggest that rather than a role in bulk synthetic processes, such as general protein synthesis, autophagy may be important in the provision of essential precursor metabolites to selected metabolic pathways under specific conditions. Such intricacy is likely a reflection of the deep integra-tion of this fundamental eukaryotic phenomenon into the core metabolism of the cell.