One of the main sources of reactive oxygen species in your skeletal muscle is the mitochondria. Damaged or dysfunctional mitochondria in particular can produce abnormally high levels of reactive oxygen species. Did you know that mitochondrial damage is associated with neurodegenerative diseases?

Reactive oxygen species cause oxidative damage (to DNA, proteins, etc.) that can lead to muscle dysfunction, especially as we age. Antioxidants, like those found in fruits and vegetables, can help scavenge and “soak up” harmful reactive oxygen species. There is growing interest in targeting antioxidants to our mitochondria to prevent or treat muscle dysfunction and damage associated with disease and injury. 

As a graduate student disentangling the molecular underpinnings of hibernation, I often lose myself in the world of cellular machinery. My favorite organelle, and perhaps the one most central to my research, is the mitochondrion (plural mitochondria).

Mouse fibroblasts (connective tissue cells). Cytoskeletons in red, nuclei in blue, and mitochondria in green. Image courtesy of the NICHD.

The mighty mitochondria

Mitochondria are commonly referred to as the “powerhouses” of the cell. These double-membrane-bound organelles produce adenosine triphosphate (ATP) via the electron transport chain. ATP, the energy currency of the cells in your body, is broken down into adenosine diphosphate (ADP) to fuel many molecular processes, including muscle contraction. Newly formed ADP is then once again “upgraded” to ATP to be used in yet another reaction. Incredibly—and this fact still amazes me—an adult recycles their body weight in ATP every day!

Reactive oxygen species and cell signaling

Although mitochondria are essential to the functioning of nearly every cell type (one exception is mature mammalian red blood cells), they come at a cost. Normal electron transport chain function within mitochondria produces reactive oxygen species (ROS), highly unstable molecules that can interact with and degrade lipids, proteins and DNA.

We’ve known for a long time that antioxidants counteract ROS-mediated damage and support muscle function. Researchers are now trying to understand how antioxidants can be specifically targeted to mitochondria in muscle cells. However, ROS aren’t just a macromolecular nuisance—they are also essential for cellular signaling. How can we best support our muscle function, especially when following a desire to stay fit and healthy, while not interfering with essential cellular signaling in skeletal muscle tissue?

Alaska blueberries are a rich source of natural antioxidants. Image courtesy of the USDA.

Non-mitochondrial sites of ROS production

A recent article published in the journal Antioxidants discusses the balance between antioxidant support and maintaining ROS-mediated cell signaling. The key to understanding antioxidant efficacy in the context of proper cell signaling is by recognizing that ROS are also produced outside of mitochondria, for example by NADPH oxidase (an enzyme complex that is involved in immune system function), xanthine oxidase (an enzyme that breaks down purines), and phospholipase A2 (an enzyme that breaks down lipids). By consuming antioxidants that are targeted specifically to our mitochondria, we can support muscle health – limiting the deleterious effects of ROS in muscle mitochondria – while allowing non-mitochondrial ROS to keep doing their job in terms of important cell signaling.

How do researchers produce mitochondria-specific antioxidants?

The article published in Antioxidants discusses some really neat science, such as how antioxidants can be “stuck” onto a lipophilic (“fat-loving”) cation (positively-charged atom or molecule). These fat-happy antioxidant vehicles shuttle across the lipid bilayer of a cell into the negatively-charged cytoplasm (the material within a cell that “holds” all of the cell’s organelles and structures). Remember learning about how opposite charges attract? The mitochondria within the cell are even more negatively-charged than the cytoplasm, so the positively-charged cations carrying the antioxidants are drawn right into the mitochondria, accumulating several hundredfolds within these organelles. Amazing!

Mitochondrial activity and reactive oxygen species are central to muscle performance. Image courtesy of the United States Navy.

Interested in reading more? Check out the article here. And if you’re curious about the benefits and risks to muscle health of antioxidant supplementation, you can check out this article. Happy reading and happy exercising!