Mentions CMT 2A: Cell biology of mitochondrial dynamics

[Guest guest]

Int Rev Cytol. 2006;254:151-213.

Cell biology of mitochondrial dynamics.Kiefel BR, Gilson PR, Beech

PL.

Mitochondria are the product of an ancient endosymbiotic event

between an alpha-proteobacterium and an archael host. An early

barrier to overcome in this relationship was the control of the

bacterium's proliferation within the host. Undoubtedly, the

bacterium (or protomitochondrion) would have used its own cell

division apparatus to divide at first and, today a remnant of this

system remains in some " ancient " and diverse eukaryotes such as

algae and amoebae, the most conserved and widespread of all

bacterial division proteins, FtsZ. In many of the eukaryotes that

still use FtsZ to constrict the mitochondria from the inside, the

mitochondria still resemble bacteria in shape and size. Eukaryotes,

however, have a mitochondrial morphology that is often highly fluid,

and in their tubular networks of mitochondria, division is clearly

complemented by mitochondrial fusion. FtsZ is no longer used by

these complex eukaryotes, and may have been replaced by other

proteins better suited to sustaining complex mitochondrial networks.

Although proteins that divide mitochondria from the inside are just

beginning to be characterized in higher eukaryotes, many division

proteins are known to act on the outside of the organelle. The most

widespread of these are the dynamin-like proteins, which appear to

have been recruited very early in the evolution of mitochondria. The

essential nature of mitochondria dictates that their loss is

intolerable to human cells, and that mutations disrupting

mitochondrial division are more likely to be fatal than result in

disease.

To date, only one disease (Charcot-Marie-Tooth disease 2A) has been

mapped to a gene that is required for mitochondrial division,

whereas two other diseases can be attributed to mutations in

mitochondrial fusion genes. Apart from playing a role in regulating

the morphology, which might be important for efficient ATP

production, research has indicated that the mitochondrial division

and fusion proteins can also be important during apoptosis;

mitochondrial fragmentation is an early triggering (and under many

stimuli, essential) step in the pathway to cell suicide.