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Spatiotemporal Analysis of Axonal Autophagosome–lysosome Dynamics Reveals Limited Fusion Events and Slow Maturation by Sydney E. Cason; Saurabh S. Mogre; Erika L. F. Holzbaur; Elena F. Koslover is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Spatiotemporal Analysis of Axonal Autophagosome–lysosome Dynamics Reveals Limited Fusion Events and Slow Maturation about?

Macroautophagy is a homeostatic process required to clear cellular waste. Neuronal autophagosomes form constitutively in the distal tip of the axon and are actively transported toward the soma, with cargo degradation initiated en route. Cargo turnover requires autophagosomes to fuse with lysosomes to acquire degradative enzymes; however, directly imaging these fusion events in the axon is impractical. Here we use a quantitative model, parameterized and validated using data from primary hippocampal neurons, to explore the autophagosome maturation process. We demonstrate that retrograde autophagosome motility is independent of fusion and that most autophagosomes fuse with only a few lysosomes during axonal transport. Our results indicate that breakdown of the inner autophagosomal membrane is much slower in neurons than in nonneuronal cell types, highlighting the importance of this late maturation step. Together, rigorous quantitative measurements and mathematical modeling elucidate the dynamics of autophagosome–lysosome interaction and autophagosomal maturation in the axon.

Who reads Spatiotemporal Analysis of Axonal Autophagosome–lysosome Dynamics Reveals Limited Fusion Events and Slow Maturation?

Author

Sydney E. Cason; Saurabh S. Mogre; Erika L. F. Holzbaur; Elena F. Koslover

Publisher

American Society for Cell Biology (ASCB)

Published

2022

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)