When cooperation fails: The office politics of mitochondria in diabetes

Author: Emily King

Teamwork in the workplace is vital. Co-workers need to support each other under pressure. When this breaks down, everything can fall apart. 

In this regard, your daily office antics are a clue to how mitochondria might cause diabetes. 

Aside from being the powerhouse of the cell, mitochondria juggle multiple responsibilities. Their role in skeletal muscle is highly stressful. Under stressful conditions, the connected network of mitochondria or “reticulum” is crucial. Mitochondria consistently look out for each other through mitochondrial fusion and fission. Fusion allows mitochondria to share healthy parts, like colleagues swapping tips. Whereas, fission isolates damaged parts, prior to repair or disposal. Fission is like taking poor-performing staff aside for a final warning. Their work will improve, or they’ll face termination of employment. When mitochondrial fusion and fission are balanced, the environment is highly productive. Muscle can do its job. 
Metabolism, a key responsibility of muscle, relies on mitochondria and sugar. After we devour our sweet treats, sugar causes the pancreas to release a hormone called insulin. Insulin then moves sugar from circulating blood into inside our cells. There, it is greeted by mitochondria and converted to fuel for bodily processes. Muscle takes up almost half of our weight and is packed full of mitochondria. It uses a lot of sugar, 80% of what’s available, to be precise. 

However, this ability of muscle is reduced in people experiencing Type 2 Diabetes. That’s one in 11 adults worldwide! Mitochondrial cooperation, or fusion, appears to have dropped. This shifts the balance more towards mitochondrial fission. The disturbed equilibrium means inefficient mitochondria, which can cause blood sugar to rise. This impact on the body is known as pre-diabetes. The body compensates by producing more insulin to drag sugar from the blood to cells. Unfortunately, this is unsustainable. It can eventually lead to insulin resistance, a key risk factor for Type 2 Diabetes. Sugar escapes to places it shouldn’t. It wears down organs, like energy levels over a long work week. Long-term blood sugar levels above the accepted range can lead to complications of diabetes. If you want healthy eyes and kidneys, plus full use of your limbs, this is not for you. 

But how do we avoid it? 

I’m asking you to reconsider your view. People with Type 2 Diabetes may not be couch potatoes or gorge to their heart’s content. Race, age, gender, genetics, and mitochondrial dysfunction can all play a part in the disease. Mitochondria don’t get to book a long weekend for rest and relaxation. They work tirelessly, at increased risk of burnout. When overworked and stressed, mitochondrial productivity can plummet, just like ours. This triggers a series of damaging events in the body that are linked to Type 2 Diabetes, cancer, and Alzheimer’s Disease.

Despite all of this, mitochondria are currently not the main focus of Type 2 Diabetes treatment. The major players are healthy nutrition and exercise. This is followed by medication for further blood sugar control. In theory, exercise studies have proven benefits for mitochondrial health. But we are real-world people, not robots! We know we *should* stick to an exercise regime, but it’s a major hurdle, even when healthy. On the diabetes drug front, metformin, the first-line choice, interacts with mitochondria, though the exact nature of this interaction is hazy.   
 
My PhD research aims to develop a new understanding of how mitochondria might cause Type 2 Diabetes. If we gain knowledge of the faulty mechanism, we can fix it. We can take steps like re-establishing fair division of labour between muscle mitochondria. By taking a new approach to treat Type 2 diabetes, we can add an extra bow to our treatment arrow aimed at this complex disease.  

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Author

​Emily King, @EKing_Sci
PhD candidate at Monash University researching mitochondria and metabolic diseases. Current teaching associate, future science writer.
​Yogi, swimmer, and reader.