Figure 3.

The unconventional roles of ATG proteins in cell death and cell division and proliferation. A) Apoptotic stimuli activate calpains and one of the substrates of these proteases is ATG5. The resulting 24 kDa truncated form of ATG5 (24K‐ATG5) associates with mitochondria and triggers cytochrome c release through a still unknown mechanism, thus participating to the initiation of the cell death programs. B) ATG12 participates in apoptosis at least in two distinct ways. First, it can become part of the ATG12‐ATG3 conjugate, which plays an important role in controlling mitochondria homeostasis and sensitizes cells to apoptosis triggered by the intrinsic mitochondrial pathway. The ATG12‐ATG3 conjugate is also stimulated upon vaccinia virus infection and it is required for the life cycle of this virus (red arrow). Second and independently from its capacity to be covalently linked to ATG5 or ATG3, ATG12 stimulates mitochondrial apoptosis through its binding and inhibition of the anti‐apoptotic function of the members of the BCL‐2 protein family. C) During mitosis BECLIN1 associates with ZWINT‐1 and mediates the interaction between the kinetochore and microtubules, a key event in cell division. Depletion of BECLIN1 causes a defect in the kinetochore protein assembling, misalignment of chromosomes and a general block in mitotic progression. D) Upon metabolic stress, ATG7 is found associated with p53 in the cytoplasm and nucleus. The nuclear complex positively regulates the expression of genes mediating the cell cycle arrest. It remains to be determined whether the nuclear ATG7‐p53 pool results from the translocation into the nucleus of the subpopulation of this complex formed in the cytoplasm (dashed arrow).