Mitophagy Antibody Sampler Kit

Autophagy is a catabolic process for the autophagosome-lysosomal degradation of bulk cytoplasmic contents (1, 2). Selective autophagy targets the degradation of distinct sets of substrates and organelles (3-5). One of the best studied examples of selective autophagy involves the clearance of damaged mitochondria through a process called mitophagy. Several pathways have been described for various contexts of mitophagy, including the FUNDC1 pathway, the BNIP3 and BNIP3L/Nix pathway, and the PINK1/Parkin pathway. FUNDC1 is a mitochondrial protein that is phosphorylated by the autophagy kinase ULK1 and regulates hypoxia induced mitophagy (6, 7). BNIP3L/Nix and BNIP3 are members of the Bcl-2 family of apoptosis regulators that are expressed on mitochondria, induced by hypoxia, and have been shown to play a role in mitophagy (8). BNIP3L/Nix is also important in the autophagic maturation of erythroid cells (9). FUNDC1, BNIP3 and BNIP3L/Nix bind to LC3 family members, targeting the mitochondria to the autophagosome.Non-hypoxic induction of mitophagy can be regulated by the PINK1/Parkin pathway, which plays causative roles in neurodegenerative disease, most notably Parkinson’s disease (10, 11). PINK1 is a mitochondrial serine/threonine kinase that is stabilized on the outer mitochondrial membrane of damaged mitochondria. Substrates of PINK1 include the E3 ubiquitin ligase Parkin and ubiquitin itself (12-14). Phosphorylation of Parkin as well as binding to phosphorylated ubiquitin leads to accumulation of ubiquitinated chains on multiple mitochondrial proteins. Ubiquitinated proteins are recognized by selective cargo receptors including SQSTM1/p62, Optineurin, and NDP52 (15-16). Autophagy cargo receptors contain an LC3-interacting region (LIR) required for binding to Atg8/LC3 family members and targeting to the autophagosome (3). 1.Reggiori, F. and Klionsky, D.J. (2002) Eukaryot Cell 1, 11-21. 2.Codogno, P. and Meijer, A.J. (2005) Cell Death Differ 12 Suppl 2, 1509-18. 3.Birgisdottir, Å.B. et al. (2013) J Cell Sci 126, 3237-47. 4.Xu, Z. et al. (2015) Acta Biochim Biophys Sin (Shanghai) 47, 571-80. 5.Mancias, J.D. and Kimmelman, A.C. (2016) J Mol Biol 428, 1659-80. 6.Liu, L. et al. (2012) Nat Cell Biol 14, 177-85. 7.Wu, W. et al. (2014) EMBO Rep 15, 566-75. 8.Sowter, H.M. et al. (2001) Cancer Res 61, 6669-73. 9.Sandoval, H. et al. (2008) Nature 454, 232-5. 10.Kitada, T. et al. (1998) Nature 392, 605-8. 11.Valente, E.M. et al. (2004) Science 304, 1158-60. 12.Kim, Y. et al. (2008) Biochem Biophys Res Commun 377, 975-80. 13.Kane, L.A. et al. (2014) J Cell Biol 205, 143-53. 14.Koyano, F. et al. (2014) Nature 510, 162-6. 15.Heo, J.M. et al. (2015) Mol Cell 60, 7-20. 16.Lazarou, M. et al. (2015) Nature 524, 309-314.