Open AccessTSG101 negatively regulates mitochondrial biogenesis in axons
Author(s) -
Tzu Huai Lin,
Dana M. Bis-Brewer,
Amy E. Sheehan,
Louise Townsend,
Daniel C. Maddison,
Stephan Züchner,
Gaynor A. Smith,
Marc Freeman
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2018770118
Subject(s) - tsg101 , mitophagy , pink1 , mitochondrion , biology , microbiology and biotechnology , biogenesis , mitochondrial fusion , parkin , mitochondrial biogenesis , proteostasis , neuroscience , mitochondrial dna , autophagy , genetics , parkinson's disease , gene , disease , medicine , apoptosis , microrna , microvesicles , pathology
Significance Mitochondrial dysfunction has been associated with many age-dependent neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease, yet understanding how a neuron maintains a pool of functional mitochondria in sufficient density and location throughout axons in vivo still remains enigmatic. Through an unbiased in vivo forward genetic screen, we identified an endosomal sorting complexes required for transport component, TSG101, as a modulator of mitochondrial number and size in neurons and provide evidence to place TSG101 as a negative regulator of mitochondrial biogenesis. We further find that TSG101 does not contribute to Parkin/Pink1-mediated mitophagy and discovered that macroautophagy regulators ATG1 and ATG6 are dispensable in axonal mitochondrial number regulation. Through in vivo screening, it is possible to unravel translatable mechanisms of axonal mitochondrial maintenance.