Wednesday, 29 October 2014

Myo19 Ensures Symmetric Partitioning of Mitochondria and Coupling of Mitochondrial Segregation to Cell Division

Jennifer L. Rohn, Jigna V. Patel, Beate Neumann, Jutta Bulkescher, Nunu Mchedlishvili, Rachel C. McMullan, Omar A. Quintero, Jan Ellenberg, Buzz Baum

At cell divison mitochondria are segregated between the halves of the cell that will form the daughter cells. In order to ensure both offspring are viable they must both be provided with a sufficient complement of functioning mitochondria. The authors use a small interfering RNA (siRNA) library to target genes known to be associated with cell division errors. The resulting phenotypes were analysed by visual inspection of videos compiled from automated microscopy images to determine which of the candidate genes led to a cell division defect.

In addition to identifying a number of already-known genes, the authors identified the myosin protein Myo19 as being crucial for cell division. Myo19 was determined to be targeted to mitochondria, where it is associated with the outer membrane through a 150 amino acid domain known as MyMOMA (Myo19-specific mitochondria outer membrane association).

Inhibiting mitochondrial fission led to a failure of cell division, which the authors hypothesise may be caused by the division ring being obstructed by an excessively fused mitochondrial network. Treatment with siRNA inhibiton of mitofusin-2 (Mfn2) rescued the Myo19 depletion phentype, lending support to this idea.

Finally, and most remarkably, Myo19 inhibition led to highly asymmetric organisation of mitochondria in anaphase. This demonstrates a role for Myo19 in the correct partitioning of mitochondria at cell division; without it mitochondria are not recruited correctly to the poles of the cell and can sometimes obstruct the division ring, causing cell division to fail. Given that mitochondria are known to move along microtubules the authors suggest that Myo19 acts as a tether, regulating their poleward movement along microtubules during segregation.

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