Mitochondrial autophagy in the control of systemic autoimmunity

SLE, however, the functional significance of this finding is not yet established. Interestingly, T cells from SLE patients have been found to be resistant to the induction of autophagy. SLE T cells harbor increased mitochondrial contents, leading to dysregulated mitochondrial functions and increased autoimmune potential in T cells. Whether increased mitochondrial accumulation is caused by defective autophagy is not determined. We found that knockouts of two Bcl-2 family members that regulate mitochondrial autophagy, Nix and Bnip3, resulted in abnormal T cell activation and the development of systemic autoimmune responses. We hypothesize that autophagy of mitochondria is essential for mitochondrial quality control in T cells, while defects in this process leads to abnormal T cell activation and the induction of systemic autoimmunity. We propose the following studies to test this hypothesis: 1. To test the hypothesis that defective mitochondrial autophagy leads to abnormal T cell activation; 2. To test the hypothesis that deficiency in defective mitochondrial autophagy in T cells leads to development of autoimmunity in vivo; and 3. To examine the molecular mechanisms for Nix and Bnip3 in mediating mitochondrial autophagy in T cells.