Mitochondrial disappearance from cells: a clue to the role of autophagy in programmed cell death and disease?

Redundant cell death mechanisms as relics and backups

“…Although it is often assumed that autophagy can participate in the effector phase of cell death (at or around the point-of-no-return), thus far there is no definitive proof that genetic ablation of Atg genes (which are required for autophagy) can prevent cell death, in spite of suggestive evidence that autophagy is indeed involved in the lethal process. 10,[52][53][54] Our provisional conclusion on this point is that caspases may participate in both the effector and the dismantling phases of apoptosis, while for autophagy only a dismantling role has been formally demonstrated. More generally, the hypothesis above predicts that in any given cell the multiplicity of cell death pathways may be greater at the dismantling than at the effector stage.…”

Mitochondria and cancer: is there a morphological connection?

“…In many cell types mitochondrial membrane permeabilization (MMP) is considered as the point of nonreturn in the cell suicide (Ferri and Kroemer, 2001). However, in sympathetic neurons for example, this event appears to be reversible and death can be circumvented downstream of cytochromic c release (Martinou et al, 1999;Deshmukh et al, 2000;Tolkovsky et al, 2002). Whether it is also the case in cancer cells remains to be determined.…”

Mitochondrial factors with dual roles in death and survival

“…Mitochondrial fragmentation and/or other morphological changes may cause or result from damage to mitochondria that subsequently leads to malfunction and degradation of mitochondria. The degradation of mitochondria was suggested to represent the commitment point in the cell death pathway in some cell types (Xue et al, 2001;Tolkovsky et al, 2002;Fannjiang et al, 2004).…”

“…Even though rho0 cells do not have oxidative phosphorylation because they lack mitochondrial DNA or have other mutations in nuclear genes that encode components of the electron transport chain, they do indeed still have mitochondria. Although these mitochondria are defective for oxygen consumption/respiration, they can generate a membrane potential, albeit reduced, as this potential is required for the import of proteins that carry out other essential biosynthetic functions unique to mitochondria (Li et al, 1995;Chandel and Schumacker, 1999;Tolkovsky et al, 2002). There are examples of cells such as erythroid cells that dispose of their mitochondria (and nuclei) through an elaborate process (involving a Bcl-2 family protein) to become erythrocytes and carry out specialized functions, but such cells are terminal and have finite lifespans (Wagner et al, 2000;Launay et al, 2005).…”