Divide et impera: Ca2+ signals, mitochondrial fission and sensitization to apoptosis

The many shapes of mitochondrial death

“…A widely accepted model anticipates that cytosolic Ca 2 þ levels increase during apoptosis by selected stimuli; and proteins that regulate apoptosis, like members of the Bcl-2 family, also influence Ca 2 þ homeostasis to control death. This model is supported for example by the finding that expression of antiapoptotic Bcl-2 and Bcl-x L as well as ablation of proapoptotic Bax and Bak reduces resting endoplasmic reticulum (ER) Ca 2 þ levels (Lam et al, 1994;FoyouziYoussefi et al, 2000;Pinton et al, 2000;Li et al, 2002;Scorrano, 2003;Bassik et al, 2004). Expression of Bax raises steady-state Ca 2 þ levels in the ER before cells are committed to die , whereas progression towards death is associated with depletion of ER stores and mitochondrial accumulation of Ca 2 þ (Nutt et al, 2002a, b).…”

Mitochondria: pharmacological manipulation of cell death

“…Proteins normally involved in mitochondrial fission and fusion may participate in MOMP (reviewed in refs. 3,13,[22][23][24]. However, this is a controversial topic, made especially challenging by the complex network of protein interactions involved in mitochondrial dynamics.…”

Quality matters: how does mitochondrial network dynamics and quality control impact on mtDNA integrity?

“…This dynamics seems indispensable for proper cellular function as many examples have shown. Reduced dynamics accompanies the process of ageing [41], is associated with the development of neurodegenerative diseases [42][43][44] and plays an important role in the execution of apoptosis [45,46]. Repetitive fusion and fission of mitochondria during the cell cycle has to be regulated [47][48][49][50]; otherwise, the continuity of the mitochondrial genome is not properly guaranteed [51,52], resulting in mitochondrial heterogeneity and malfunction [53].…”