Cardiomyocyte-intrinsic somatic mtDNA mutations induce an OXPHOS-dependent immune response and promote progressive heart failure.

Kristina Bubb, Giovanni Rigoni, Polyxeni Papadea, Gianluigi Pironti, Jelena Misic, Shan Jiang, David Alsina, Diana Rubalcava-Gracia, Daniel C Andersson, Roberta Filograna, Camilla Koolmeister, Patrick Giavalisco, Anna Wredenberg, Matthias Mann, Florian A Rosenberger, Nils-Göran Larsson

Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. · pubmed

Paper

Abstract

Mitochondrial DNA (mtDNA) mutations accumulate with age, but their mechanistic contribution to aging remains unclear. The classical mtDNA mutator mouse expresses a proofreading-deficient mtDNA polymerase (POLG

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Research summary

Cardiomyocyte-intrinsic somatic mtDNA mutations induce an OXPHOS-dependent immune response that drives progressive heart failure. This paper is relevant because it elucidates a specific mechanistic pathway by which the accumulation of somatic mitochondrial DNA mutations—a hallmark of aging—contributes to age-related organ dysfunction, thereby identifying a potential target for intervening in the root causes of aging-related pathology rather than just treating symptoms.

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