Mitochondrial signaling in the vascular endothelium: beyond reactive oxygen species

  • Andrew O. Kadlec
  • Andreas M. Beyer
  • Karima Ait-Aissa
  • David D. GuttermanEmail author
Invited Review


Traditionally, the mitochondria have been viewed as the cell’s powerhouse, producing energy in the form of ATP. As a byproduct of ATP formation, the mitochondrial electron transport chain produces substantial amounts of reactive oxygen species (ROS). First thought to be toxic, recent literature indicates an important signaling function for mitochondria-derived ROS, especially in relation to cardiovascular disease pathogenesis. This has spawned an evolution to a more contemporary view of mitochondrial function as a dynamic organelle involved in key regulatory and cell survival processes. Beyond ROS, recent studies have identified a host of mitochondria-linked factors that influence the cellular and extracellular environments, including mitochondria-derived peptides, mitochondria-localized proteins, and the mitochondrial genome itself. Interestingly, many of these factors help orchestrate ROS homeostasis and ROS-related signaling. The paradigm defining the role of mitochondria in the vasculature needs to be updated yet again to include these key signaling factors, which serves as the focus of the current review. In describing these novel signaling factors, we pay specific attention to their influence on endothelial homeostasis. Therapies targeting these pathways are discussed, as are emerging research directions.


Mitochondria Cardiovascular disease Endothelium Reactive oxygen species 



We thank Dr. Michael Widlansky, Dr. David Zhang, Dr. Neil Hogg, and Dawid Chabowski for providing excellent critical input on this manuscript.

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Andrew O. Kadlec
    • 1
    • 3
  • Andreas M. Beyer
    • 1
    • 2
    • 3
  • Karima Ait-Aissa
    • 1
    • 2
    • 3
  • David D. Gutterman
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Department of PhysiologyMedical College of WisconsinMilwaukeeUSA
  2. 2.Division of Cardiology, Cardiovascular Center, Department of MedicineMedical College of WisconsinMilwaukeeUSA
  3. 3.Cardiovascular CenterMedical College of WisconsinMilwaukeeUSA
  4. 4.Department of Veterans Administration Medical CenterMilwaukeeUSA

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