@article{2c7aa8a2640e497db0f0f60db147886b,
title = "MitoTimer probe reveals the impact of autophagy, fusion, and motility on subcellular distribution of young and old mitochondrial protein and on relative mitochondrial protein age",
abstract = "To study mitochondrial protein age dynamics, we targeted a time-sensitive fluorescent protein, MitoTimer, to the mitochondrial matrix. Mitochondrial age was revealed by the integrated portions of young (green) and old (red) MitoTimer protein. Mitochondrial protein age was dependent on turnover rates as pulsed synthesis, decreased import, or autophagic inhibition all increased the proportion of aged MitoTimer protein. Mitochondrial fusion promotes the distribution of young mitochondrial protein across the mitochondrial network as cells lacking essential fusion genes Mfn1 and Mfn2 displayed increased heterogeneity in mitochondrial protein age. Experiments in hippocampal neurons illustrate that the distribution of older and younger mitochondrial protein within the cell is determined by subcellular spatial organization and compartmentalization of mitochondria into neurites and soma. This effect was altered by overexpression of mitochondrial transport protein, RHOT1/MIRO1. Collectively our data show that distribution of young and old protein in the mitochondrial network is dependent on turnover, fusion, and transport.",
keywords = "Aging, Autophagy, MitoTimer, Mitochondrial dynamics, RHOT1",
author = "Ferree, {Andrew W.} and Kyle Trudeau and Eden Zik and Benador, {Ilan Y.} and Gilad Twig and Gottlieb, {Roberta A.} and Shirihai, {Orian S.}",
note = "Funding Information: We would like to thank Drs Barbara Corkey, Marc Liesa, Fernanda Cerquiera, and Robert Screaton for sharing their insights. We thank Dr Mike Kirber for his help with imaging and image analysis. We thank Abbie Newby-Kew for her guidance and assistance with hippocampal neurons cultures. We thank Dr Thomas Schwarz and his lab members for the kind gift of the RHOT1 constructs, and to Drs Gyorgy Hajnoczky and David Chan and their labs for providing the Mfn1/2 KO MEFs. We would like to express gratitude to Dr Janice Weinberg for her statistical analysis guidance and to Professor Daniel Dagan for his continued generosity and supreme editing skills. We would also like to thank Christine Hanko for spectral analysis of the Timer, and Erga Rivis Studio for help in graphic design. KT was supported by a National Science Foundation Graduate Research Fellowship under Grant No. DGE-0741448, and Levinsky Fellowship from the department of Medicine at Boston University School of Medicine. OSS is funded by NIH grants RO1 DK35914, R01 DK56690, and R01 DK074778.",
year = "2013",
month = jan,
day = "1",
doi = "10.4161/auto.26503",
language = "English",
volume = "9",
pages = "1887--1896",
journal = "Autophagy",
issn = "1554-8627",
publisher = "Taylor and Francis Ltd.",
number = "11",
}