biostudies-literatureUnknown16Heo KNational Institutes of HealthMichael J. Fox Foundation for Parkinson's ResearchMicrotubule-based transport provides mitochondria to distant regions of neurons and is essential for neuronal health. To identify compounds that increase mitochondrial motility, we screened 1,641 small-molecules in a high-throughput screening platform. Indirubin and cantharidin increased mitochondrial motility in rat cortical neurons. Cantharidin is known to inhibit protein phosphatase 2A (PP2A). We therefore tested two other inhibitors of PP2A: LB-100 and okadaic acid. LB-100 increased mitochondrial motility, but okadaic acid did not. To resolve this discrepancy, we knocked down expression of the catalytic subunit of PP2A (PP2CA). This long-term inhibition of PP2A more than doubled retrograde transport of axonal mitochondria, confirming the importance of PP2A as a regulator of mitochondriFrontiers in cellular neuroscience852245https://www.ebi.ac.uk/biostudies/studies/S-EPMC8973303biostudies-literatureSerine/Threonine Protein Phosphatase 2A Regulates the Transport of Axonal Mitochondria.PMC8973303Schwarz TLBasu HGutnick AHeo KWei WShlevkov EfalseSerine/Threonine Protein Phosphatase 2A Regulates the Transport of Axonal Mitochondria.Microtubule-based transport provides mitochondria to distant regions of neurons and is essential for neuronal health. To identify compounds that increase mitochondrial motility, we screened 1,641 small-molecules in a high-throughput screening platform. Indirubin and cantharidin increased mitochondrial motility in rat cortical neurons. Cantharidin is known to inhibit protein phosphatase 2A (PP2A). We therefore tested two other inhibitors of PP2A: LB-100 and okadaic acid. LB-100 increased mitochondrial motility, but okadaic acid did not. To resolve this discrepancy, we knocked down expression of the catalytic subunit of PP2A (PP2CA). This long-term inhibition of PP2A more than doubled retrograde transport of axonal mitochondria, confirming the importance of PP2A as a regulator of mitochondri2022-01-01T00:00:00Z20222025-04-26T15:20:40.031Z2025-04-06T14:50:53.554ZS-EPMC89733033537056310.3389/fncel.2022.852245