Mitochondrial epigenetics in aging and cardiovascular diseases

Alessia Mongelli; Alessandro Mengozzi; Martin Geiger; Era Gorica; Shafeeq Ahmed Mohammed; Francesco Paneni; Frank Ruschitzka; Sarah Costantino

doi:10.3389/fcvm.2023.1204483

Mitochondrial epigenetics in aging and cardiovascular diseases

Front Cardiovasc Med. 2023 Jul 13:10:1204483. doi: 10.3389/fcvm.2023.1204483. eCollection 2023.

Authors

Alessia Mongelli¹, Alessandro Mengozzi¹, Martin Geiger¹, Era Gorica¹, Shafeeq Ahmed Mohammed¹, Francesco Paneni^{1

2}, Frank Ruschitzka^{1

2}, Sarah Costantino^{1

2}

Affiliations

¹ Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital and University of Zürich, Zurich, Switzerland.
² Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Abstract

Mitochondria are cellular organelles which generate adenosine triphosphate (ATP) molecules for the maintenance of cellular energy through the oxidative phosphorylation. They also regulate a variety of cellular processes including apoptosis and metabolism. Of interest, the inner part of mitochondria-the mitochondrial matrix-contains a circular molecule of DNA (mtDNA) characterised by its own transcriptional machinery. As with genomic DNA, mtDNA may also undergo nucleotide mutations that have been shown to be responsible for mitochondrial dysfunction. During physiological aging, the mitochondrial membrane potential declines and associates with enhanced mitophagy to avoid the accumulation of damaged organelles. Moreover, if the dysfunctional mitochondria are not properly cleared, this could lead to cellular dysfunction and subsequent development of several comorbidities such as cardiovascular diseases (CVDs), diabetes, respiratory and cardiovascular diseases as well as inflammatory disorders and psychiatric diseases. As reported for genomic DNA, mtDNA is also amenable to chemical modifications, namely DNA methylation. Changes in mtDNA methylation have shown to be associated with altered transcriptional programs and mitochondrial dysfunction during aging. In addition, other epigenetic signals have been observed in mitochondria, in particular the interaction between mtDNA methylation and non-coding RNAs. Mitoepigenetic modifications are also involved in the pathogenesis of CVDs where oxygen chain disruption, mitochondrial fission, and ROS formation alter cardiac energy metabolism leading to hypertrophy, hypertension, heart failure and ischemia/reperfusion injury. In the present review, we summarize current evidence on the growing importance of epigenetic changes as modulator of mitochondrial function in aging. A better understanding of the mitochondrial epigenetic landscape may pave the way for personalized therapies to prevent age-related diseases.

Keywords: aging; cardiovascular diseases; methylation; mitochondria; mitoepigenetics; mtDNA; ncRNAs.

Publication types

Review

Grants and funding

AM is the recipient of an International Grant from the Italian Society of Arterial Hypertension. SAM is the recipients of a Forschungskredit Candoc grant from the University of Zürich. FP is the recipient of a H.H. Sheikh Khalifa bin Hamad Al Thani Foundation Assistant Professorship at the Faculty of Medicine, University of Zürich. This work was supported by the Swiss National Science Foundation (n. 310030_197557), the Swiss Heart Foundation (n. FF19045), the Stiftung für wissenschaftliche Forschung, the Olga Mayenfisch Foundation, the Swiss Life Foundation, the Kurt und Senta-Hermann Stiftung, the EMDO Stiftung and the Schweizerische Diabetes-Stiftung (to FP); and the Holcim Foundation, the Swiss Heart Foundation, the Swiss Life Foundation and the Gebauer Stiftung (to SC).