Agah

Alexander

Brand

Cassidy-Stone

Chen

Clary Clish

David C. Chan

Delettre

Dorn

Friedman

Gandre-Babbe

Harvey

Hayashi

Hsiuchen Chen

Ikeda

Ishihara

J. Michael McCaffery

Kageyama

Kasahara

Lopaschuk

Losón

Mishra

Mohit Jain

Otera

Papanicolaou

Postic

Sadate-Ngatchou

Shamseldin

Shuxun Ren

Song

Vamsi Mootha

Wakabayashi

Waterham

Züchner

Defects in mitochondrial fusion or fission are associated with many pathologies, raising the hope that pharmacological manipulation of mitochondrial dynamics may have therapeutic benefit. This approach assumes that organ physiology can be restored by rebalancing mitochondrial dynamics, but this concept remains to be validated. We addressed this issue by analyzing mice deficient in Mff, a protein important for mitochondrial fission. Mff mutant mice die at 13 wk as a result of severe dilated cardiomyopathy leading to heart failure. Mutant tissue showed reduced mitochondrial density and respiratory chain activity along with increased mitophagy. Remarkably, concomitant deletion of the mitochondrial fusion gene Mfn1 completely rescued heart dysfunction, life span, and respiratory chain function. Our results show for the first time that retuning the balance of mitochondrial fusion and fission can restore tissue integrity and mitochondrial physiology at the whole-organ level. Examination of liver, testis, and cerebellum suggest, however, that the precise balance point of fusion and fission is cell type specific.</jats:p

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The Journal of Cell Biology

Titration of mitochondrial fusion rescues Mff-deficient cardiomyopathy

http://jcb.rupress.org/content/jcb/211/4/795.full.pdf

Titration of mitochondrial fusion rescues Mff-deficient cardiomyopathy

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