Benan John Mathai

• Munson, Michael Joseph; Mathai, Benan John; Ng, Matthew; Trachsel Moncho, Laura Cristina; de la Ballina, Laura R & Simonsen, Anne Gjøen (2022). GAK and PRKCD kinases regulate basal mitophagy. Autophagy. ISSN 1554-8627. 18(2), p. 467–469. doi: 10.1080/15548627.2021.2015154. Full text in Research Archive
• Munson, Michael Joseph; Mathai, Benan J.; Ng, Matthew; Trachsel Moncho, Laura Cristina; de la Ballina, Laura R & Schultz, Sebastian W. [Show all 13 contributors for this article] (2021). GAK and PRKCD are positive regulators of PRKN-independent mitophagy. Nature Communications. ISSN 2041-1723. 12(1). doi: 10.1038/s41467-021-26331-7. Full text in Research Archive Show summary

  The mechanisms involved in programmed or damage-induced removal of mitochondria by mitophagy remains elusive. Here, we have screened for regulators of PRKN-independent mitophagy using an siRNA library targeting 197 proteins containing lipid interacting domains. We identify Cyclin G-associated kinase (GAK) and Protein Kinase C Delta (PRKCD) as regulators of PRKN-independent mitophagy, with both being dispensable for PRKN- dependent mitophagy and starvation-induced autophagy. We demonstrate that the kinase activity of both GAK and PRKCD are required for efficient mitophagy in vitro, that PRKCD is present on mitochondria, and that PRKCD facilitates recruitment of ULK1/ATG13 to early autophagic structures. Importantly, we demonstrate in vivo relevance for both kinases in the regulation of basal mitophagy. Knockdown of GAK homologue (gakh-1) in C. elegans or knockout of PRKCD homologues in zebrafish led to significant inhibition of basal mitophagy, highlighting the evolutionary relevance of these kinases in mitophagy regulation.

• Gawel, Kinga Aurelia; Turski, Waldemar A.; van der Ent, Wietske; Mathai, Benan John; Kirstein-Smardzewska, Karolina Joanna & Simonsen, Anne [Show all 7 contributors for this article] (2020). Phenotypic Characterization of Larval Zebrafish (Danio rerio) with Partial Knockdown of the cacna1a Gene. Molecular Neurobiology. ISSN 0893-7648. 57(4). doi: 10.1007/s12035-019-01860-x. Show summary

  The CACNA1A gene encodes the pore-forming α1 subunit of voltage-gated P/Q type Ca2+ channels (Cav2.1). Mutations in this gene, among others, have been described in patients and rodents suffering from absence seizures and episodic ataxia type 2 with/without concomitant seizures. In this study, we aimed for the first time to assess phenotypic and behavioral alterations in larval zebrafish with partial cacna1aa knockdown, placing special emphasis on changes in epileptiform-like electrographic discharges in larval brains. Whole-mount in situ hybridization analysis revealed expression of cacna1aa in the optic tectum and medulla oblongata of larval zebrafish at 4 and 5 days post-fertilization. Next, microinjection of two antisense morpholino oligomers (individually or in combination) targeting all splice variants of cacna1aa into fertilized zebrafish eggs resulted in dose-dependent mortality and decreased or absent touch response. Over 90% knockdown of cacna1aa on protein level induced epileptiform-like discharges in the optic tectum of larval zebrafish brains. Incubation of morphants with antiseizure drugs (sodium valproate, ethosuximide, lamotrigine, topiramate) significantly decreased the number and, in some cases, cumulative duration of epileptiform-like discharges. In this context, sodium valproate seemed to be the least effective. Carbamazepine did not affect the number and duration of epileptiform-like discharges. Altogether, our data indicate that cacna1aa loss-of-function zebrafish may be considered a new model of absence epilepsy and may prove useful both for the investigation of Cacna1a-mediated epileptogenesis and for in vivo drug screening.

• Gawel, Kinga Aurelia; Turski, Waldemar A.; van der Ent, Wietske; Mathai, Benan John; Kirstein-Smardzewska, Karolina Joanna & Simonsen, Anne [Show all 7 contributors for this article] (2019). Phenotypic Characterization of Larval Zebrafish (Danio rerio) with Partial Knockdown of the cacna1a Gene . Molecular Neurobiology. ISSN 0893-7648. doi: 10.1007/s12035-019-01860-x. Full text in Research Archive
• Abudu, Yakubu Princely; Pankiv, Serhiy; Mathai, Benan John; Lamark, Trond; Johansen, Terje & Simonsen, Anne (2019). NIPSNAP1 and NIPSNAP2 act as “eat me” signals to allow sustained recruitment of autophagy receptors during mitophagy. Autophagy. ISSN 1554-8627. doi: 10.1080/15548627.2019.1637642.
• Abudu, Yakubu Princely; Pankiv, Serhiy; Mathai, Benan John; Lystad, Alf Håkon; Bindesbøll, Christian & Brenne, Hanne Britt [Show all 14 contributors for this article] (2019). NIPSNAP1 and NIPSNAP2 act as “eat-me signal” for mitophagy. Developmental Cell. ISSN 1534-5807. 49(4), p. 509–525.e12. doi: 10.1016/j.devcel.2019.03.013. Full text in Research Archive
• Simonsen, Anne; Mathai, Benan John & Meijer, Annemarie (2017). Studying Autophagy in Zebrafish. Cells. ISSN 2073-4409. 6(3). doi: 10.3390/cells6030021. Full text in Research Archive
• Holland, Petter; Knævelsrud, Helene; Søreng, Kristiane; Mathai, Benan John; Lystad, Alf Håkon & Pankiv, Serhiy [Show all 16 contributors for this article] (2016). HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels. Nature Communications. ISSN 2041-1723. 7. doi: 10.1038/ncomms13889. Full text in Research Archive

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