title: Fluctuation-driven mechanotransduction regulates mitochondrial-network structure and function.
abstract: Cells can be exposed to irregular mechanical fluctuations, such as those arising from changes in blood pressure. Here, we report that ATP production, assessed through changes in mitochondrial membrane potential, is downregulated in vascular smooth muscle cells in culture exposed to monotonous stretch cycles when compared with cells exposed to a variable cyclic stretch that incorporates physiological levels of cycle-by-cycle variability in stretch amplitude. Variable stretch enhances ATP production by increasing the expression of ATP synthase's catalytic domain, cytochrome c oxidase and its tyrosine phosphorylation, mitofusins and PGC-1α. Such a fluctuation-driven mechanotransduction mechanism is mediated by motor proteins and by the enhancement of microtubule-, actin- and mitochondrial-network complexity. We also show that, in aorta rings isolated from rats, monotonous stretch downregulates-whereas variable stretch maintains-physiological vessel-wall contractility through mitochondrial ATP production. Our results have implications for ATP-dependent and mechanosensitive intracellular processes.
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Bartolák-Suki
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Imsirovic
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.
authors.forename: Harikrishnan
authors.initials: H
authors.lastname: Parameswaran
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Wellman
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.
authors.forename: Nuria
authors.initials: N
authors.lastname: Martinez
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Allen
authors.affiliation: University Children's Hospital Basel, CH-4031 Basel, Switzerland.
authors.forename: Urs
authors.initials: U
authors.lastname: Frey
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.
authors.forename: Béla
authors.initials: B
authors.lastname: Suki
mesh_terms: D025181:ATP Synthetase Complexes / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry; D000293:Adolescent; D000328:Adult; D000818:Animals; D001011:Aorta / Q000473:pathology; D020134:Catalytic Domain; D002417:Cattle; D003576:Electron Transport Complex IV / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology; D008564:Membrane Potentials; D008875:Middle Aged; D008928:Mitochondria / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation; D051381:Rats; D013314:Stress, Mechanical; D014157:Transcription Factors / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry; D055815:Young Adult
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D014443:Tyrosine; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D025181:ATP Synthetase Complexes; D020558:GTP Phosphohydrolases; C470017:Mfn1 protein, human