Trudeau 2014 Abstract MiP2014
|Role of mitochondrial fusion and motility in distributing young mitochondrial protein and removing old protein from the mitochondrial network.|
Mitochondrial fusion and fission have been shown to allow for the equilibration of protein across the mitochondrial population as well as coordinate autophagy-mediated removal of defective mitochondria . We hypothesized that mitochondrial fusion is serving a role in shuttling newly synthesized proteins from a subset of mitochondria that import them to the rest of the mitochondrial population, thereby determining distribution of young and old protein within the network.
We assessed mitochondrial protein age by targeting a time-sensitive fluorescent protein, MitoTimer, to the mitochondrial matrix. Emitted fluorescence of a newly translated timer is green and over time the emission shifts to red . We fused the fluorescent timer to the mitochondrial targeting sequence of the Cox8a subunit, to form the MitoTimer construct.
Mitochondrial protein age, a result of equilibrated young and old proteins, was dependent on turnover rates as pulsed synthesis or autophagic inhibition increased the proportion of old MitoTimer protein. Mitochondrial fusion promotes the distribution of young mitochondrial protein across the mitochondrial network as cells lacking essential fusion genes Mfn1 and Mfn2, or down-regulated Opa1, displayed increased heterogeneity in mitochondrial protein age and accumulation of mitochondria with old protein. Experiments in hippocampal neurons illustrate that intracellular spatial organization also impairs distribution of young mitochondrial material and this effect was reduced by over-expression of mitochondrial transport protein, Miro1.
Collectively our data show that equilibration of young and old protein in the mitochondrial network is dependent on mitochondrial turnover, fusion, and transport.
Labels: MiParea: mt-Structure;fission;fusion Event: A2, P-flash Additional: MiP2014
1-Dep Medicine, Obesity Nutrition Section, Evans Biomed Research Center, Boston Univ School Med, MA, USA; 2-Donald P. Shiley Biosc Center, San Diego State Univ, CA, USA. - firstname.lastname@example.org
References and acknowledgements
Supported by: National Science Foundation Graduate Research Fellowship.
- Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, Stiles L, Haigh SE, Katz S, Las G, Alroy J, Wu M, Py BF, Yuan J, Deeney JT, Corkey BE, Shirihai OS (2008) Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 27: 433-46.
- Terskikh A, Fradkov A, Ermakova G, Zaraisky A, Tan P, Kajava AV, Zhao X, Lukyanov S, Matz M, Kim S, Weissman I, Siebert P (2000) 'Fluorescent timer': protein that changes color with time. Science 290: 1585-8.