Dr. Josefa Steinhauer, associate professor of biology, recently published a study in PLOS ONE titled “” (Sept. 10, 2021). Along with Dr. Steinhauer, the article is co-authored Dr. Surya Jyoti Banerjee and Adina Schonbrun ’15S (currently a graduate student at Memorial Sloan Kettering Cancer Center), with contributions from the following: Sogol Eizadshenass (a post-master’s student employed by Dr. Steinhauer), Shimshon Benji ’21YC, Yaakov Tzvi Cantor ’21YC, Liam Eliach ’20YC, Matthew Lubin ’16YC, Zev Narrowe ’20YC, Jeremy Purow ’22YC, Benjamin Shulman ’19YC and Leib Wiener ’21YC. Here is the abstract:

Neurodegenerative disease (ND) is a growing health burden worldwide, but its causes and treatments remain elusive. Although most cases of ND are sporadic, rare familial cases have been attributed to single genes, which can be investigated in animal models. We have generated a new mutation in the calcium-independent phospholipase A₂ (iPLA₂) VIA gene CG6718, the Drosophila melanogaster ortholog of human PLA2G6/PARK14, mutations in which cause a suite of NDs collectively called PLA2G6-associated neurodegeneration (PLAN). Our mutants display age-related loss of climbing ability, a symptom of neurodegeneration in flies. Although phospholipase activity commonly is presumed to underlie iPLA₂-VIA function, locomotor decline in our mutants is rescued by a transgene carrying a serine-to-alanine mutation in the catalytic residue, suggesting that important functional aspects are independent of phospholipase activity. Additionally, we find that iPLA₂-VIA knockdown in either muscle or neurons phenocopies locomotor decline with age, demonstrating its necessity in both neuronal and non-neuronal tissues. Furthermore, RNA in situ hybridization shows high endogenous iPLA₂-VIA mRNA expression in adult germ cells, and transgenic HA-tagged iPLA₂-VIA colocalizes with mitochondria there. Mutant males are fertile with normal spermatogenesis, while fertility is reduced in mutant females. Mutant female germ cells display age-related mitochondrial aggregation, loss of mitochondrial potential, and elevated cell death. These results suggest that iPLA₂-VIA is critical for mitochondrial integrity in the Drosophila female germline, which may provide a novel context to investigate its functions with parallels to PLAN.

“The work done by my lab,” said Dr. Steinhauer, “shows that a human disease gene for neurodegeneration and parkinsonism (iPLA2-6A) exhibits the same types of disease symptoms when mutated in fruit flies. Thus, the tiny fly can be used as a model to understand what goes wrong in patients with variants of this gene. This publication shows that iPLA2-6A is needed not only in the nerve cells of the brain, but in other cells as well, including muscles and the germ cells (which produce gametes), for flies to stay healthy into old age.”