Question: Activation of Fas activates caspase-8 which triggers the extrinsic pathway of apoptosis. In some …

Activation of Fas activates caspase-8 which triggers the
extrinsic pathway of apoptosis. In some cells the activation of Fas
also engages the intrinsic pathway of apoptosis. In these cells,
caspase-8 cleaves the protein Bid to produce an active fragment,
tBid, that binds to the mitochondrial membrane. tBid promotes
oligomerization of Bax and of Bak, which stimulates the release of
cytochrome c into the cytosol to trigger events leading to
apoptosis (see Fig. 1 below). To study this pathway in more detail,
you’ve generated mouse embryo fibroblasts (MEFs) that are Bax-/- ,
Bak-/- , or Bax-/- Bak-/- . You have also constructed a vector that
expresses tBid so that you can study the process independent of
Fas. In untreated MEFs and in MEFs treated with the empty vector
(it means the vector does not contain the tBid gene), very few
cells undergo apoptosis (Fig. 2). By contrast, when MEFs are
treated with the vector that expresses tBid, the wild-type cells
and the cells individually defective for Bax or Bak show a dramatic
increase in apoptotic cells. MEFs that are defective for both Bax
and Bak, however, show no increase in the number of apoptotic cells
(Fig. 2). Among the various mutant cells, cytochrome c is retained
in the mitochondria only in the Bax-/- Bak-/- MEFs treated with
tBid. Question: Imagine that you could microinject
cytochrome c into the cytosol of wild-type cells and of cells that
were doubly defective for Bax and Bak. Would you expect one, both,
or neither type of cell to undergo apoptosis? Explain your
reasoning.