Autophagy proteins LC3B, ATG5 and ATG12 participate in quality control after mitochondrial damage and influence life span

Institute for Cell Biology and Neuroscience, Center of Excellence Frankfurt-Macromolecular Complexes, Goethe University, Frankfurt/Main, Germany.
Autophagy (Impact Factor: 11.75). 01/2012; 8(1):47-62. DOI: 10.4161/auto.8.1.18174
Source: PubMed


Mitochondrial health is maintained by the quality control mechanisms of mitochondrial dynamics (fission and fusion) and mitophagy. Decline of these processes is thought to contribute to aging and neurodegenerative diseases. To investigate the role of mitochondrial quality control in aging on the cellular level, human umbilical vein endothelial cells (HUVEC) were subjected to mitochondria-targeted damage by combining staining of mitochondria and irradiation. This treatment induced a short boost of reactive oxygen species, which resulted in transient fragmentation of mitochondria followed by mitophagy, while mitochondrial dynamics were impaired. Furthermore, targeted mitochondrial damage upregulated autophagy factors LC3B, ATG5 and ATG12. Consequently these proteins were overexpressed in HUVEC as an in vitro aging model, which significantly enhanced the replicative life span up to 150% and the number of population doublings up to 200%, whereas overexpression of LAMP-1 did not alter the life span. Overexpression of LC3B, ATG5 and ATG12 resulted in an improved mitochondrial membrane potential, enhanced ATP production and generated anti-apoptotic effects, while ROS levels remained unchanged and the amount of oxidized proteins increased. Taken together, these data relate LC3B, ATG5 and ATG12 to mitochondrial quality control after oxidative damage, and to cellular longevity.

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    • "Oxidative damage induced by mitochondria-targeted irradiation of ECs promotes Parkin translocation to depolarized mitochondria and increases LC3-II level and autophagosome formation (Mai et al., 2012). When exposed to hemin, ECs undergo lipid peroxidation, leading to mitochondria depolarization and mitophagy (Higdon et al., 2012). "
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    • "Cloning of PINK1-GFP [21], PINK1G309D-GFP [21], GFP-Parkin [15], GFP-LC3 [15], and LAMP-1-GFP [15] was described before. Transient knockdown of PINK1 was achieved with PINK1 antisense RNA (HS_PINK1_4_HP_Validated siRNA, Qiagen) and Allstars Negative Control (scrambled) siRNA (Qiagen) was used as control. "
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