In Drosophila melanogaster, loss-of-function mutations in either Pink1 or Parkin show similar phenotypes including impaired ability to fly, male sterility, and degeneration of dopaminergic neurons. Transgenic overexpression of Parkin in mutants lacking Pink1 significantly ameliorates the loss-of-function phenotype, but overexpression of Pink1 cannot rescue the Parkin loss-of-function phenotype. According to these findings, which protein is more likely to act upstream of the other one? Assuming that the Parkin loss-of-function phenotype is merely due to defects in autophagy, would you expect Parkin overexpression to also rescue an ATG9 loss-of-function phenotype?

Question

Quizplus · Accepted Answer

Overexpression of a protein in a pathway can often rescue the loss of function of upstream (but not downstream) proteins. Since ATG9 is involved in downstream steps of mitophagy, Parkin overexpression is not expected to rescue an ATG9 loss-of-function phenotype.

In Drosophila Melanogaster, Loss-Of-Function Mutations in Either Pink1 or Parkin