Lysosomes solve fundamental obstacles to the evolution of complex life forms. Lysosomes sense and maintain cellular metabolic stores and ensure their judicious use. More importantly, lysosomes respond to changes in osmotic conditions to maintain the membrane, which protects life from the harsh realities of the second law of thermodynamics. The primordial imperatives of the first and second law of thermodynamics underlie the evolution of the processes regulating membrane traffic. In order to meet the needs of maintenance of membrane integrity and osmotic stress with energy production, the endo-lysosomal fusion machinery integrates information from the metabolic and osmotic state of the cell to regulate fusion activity of the endosome and receptor recycling.Membrane lipids orchestrate the processes of endo-lysosomal maturation. This Dissertation identified lipid modifiers that regulate endolysosomal maturation in response to metabolism and osmotic stress. We then manipulated these conditions in order to probe how the membrane lipid environment controls the subunit associations and function of the endo-lysosomal machinery and the guanine nucleotide exchange factor Mon1-Ccz1Endo-lysosomal dynamics have evolved to impact diverse physiological processes including, retrograde axonal transport(Deinhardt et al., 2006), and immune activation and antigen loading on MHC-II(Fairn and Grinstein, 2012) and cellular signaling systems such as insulin(Lodhi et al., 2008) and Wnt(Taelman et al., 2010).By examining the mechanisms of control in their evolutionary context, one gains a better understanding of a complicated cellular process underlying diseases such as autoimmunity, Alzheimer’s disease, and Diabetes Mellitus.
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Primordial imperatives and the evolution of control of endolysosomal trafficking
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