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Cell Metab ; 33(7): 1322-1341.e13, 2021 07 06.
Article in English | MEDLINE | ID: mdl-34019840

ABSTRACT

Mitochondria control eukaryotic cell fate by producing the energy needed to support life and the signals required to execute programed cell death. The biochemical milieu is known to affect mitochondrial function and contribute to the dysfunctional mitochondrial phenotypes implicated in cancer and the morbidities of aging. However, the physical characteristics of the extracellular matrix are also altered in cancerous and aging tissues. Here, we demonstrate that cells sense the physical properties of the extracellular matrix and activate a mitochondrial stress response that adaptively tunes mitochondrial function via solute carrier family 9 member A1-dependent ion exchange and heat shock factor 1-dependent transcription. Overall, our data indicate that adhesion-mediated mechanosignaling may play an unappreciated role in the altered mitochondrial functions observed in aging and cancer.


Subject(s)
Cell Adhesion/physiology , Mechanotransduction, Cellular/physiology , Mitochondrial Dynamics/physiology , Adult , Animals , Animals, Genetically Modified , Caenorhabditis elegans , Cell Respiration , Cells, Cultured , Extracellular Matrix/metabolism , Female , HEK293 Cells , Humans , Hyperglycemia/metabolism , Hyperglycemia/pathology , Hyperglycemia/physiopathology , Integrins/physiology , Ion Exchange , Mice , Microscopy, Confocal , Middle Aged , Mitochondria/metabolism , Mitochondria/physiology , Oxidative Stress/physiology , Reactive Oxygen Species/metabolism , Signal Transduction/physiology , Sodium-Hydrogen Exchanger 1/physiology , Time-Lapse Imaging
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