Understanding Mitochondrial Adaptations to Cellular Metabolism

Employing advanced super-resolution microscopes, scientists from the University of California, Irvine, and the University of Pennsylvania have, for the inaugural time, witnessed the processes of electrical charge and discharge within mitochondria extracted from cells.

A mitochondrion, found within a cell, employs aerobic respiration to produce adenosine triphosphate (ATP), an organic compound crucial for supplying energy to various processes in living tissues.

Researchers in the medical and biomedical engineering fields have been striving to enhance their comprehension of mitochondria, recognizing their significance in human health and disease.

While prior research projects have focused on the physical characteristics of these components within living cells, the UCI-led project marks the first utilization of super-resolution microscopes to investigate live, extracellular mitochondria.

By observing alterations in mitochondrial membranes during different metabolic states, the researchers were able to witness the electrophysiological functions of these living organelles. The team’s findings were published in the journal ACS Nano.

When we first started studying isolated mitochondria, we knew they behaved like a battery based on some work from the Tokyo Metropolitan Institute of Gerontology and UCLA, but we could not control them very well inside the cell to probe them. Now we can control each individual electrical component and cause it to charge and discharge.”

Peter Burke, Study Co-Author and Professor, Electrical Engineering and Computer Science, University of California-Irvine

Burke mentioned that the advancements were facilitated by the latest super-resolution microscopes.

The team utilized all three primary methods—Airy microscopy, stimulated emission depletion microscopy, and lattice structured illumination microscopy—in their investigation. This approach allowed them to scrutinize cristae, which are repetitive serpentine structures within mitochondria measuring approximately 100 nm.

Burke explained that since the shortest wavelength of visible light is violet at around 380 nm, they required potent instruments, namely super-resolution microscopes, to delve into the voltage distribution of structures smaller than a third of that size.

Imagine trying to study how the battery pack in a Tesla works, but you can only do it by driving the car. You would not learn much about the battery pack inside the car.”

Peter Burke, Study Co-Author and Professor, Electrical Engineering and Computer Science, University of California-Irvine

By extracting mitochondria from the cell and maintaining their viability, Burke and his collaborators, including lead author ChiaHung Lee (a UCI Graduate Student Researcher in Biomedical Engineering) and Douglas Wallace of the University of Pennsylvania, successfully induced the charging and discharging processes in the mitochondria.

We could observe in detail how each individual part behaved as a single battery, much like how battery packs in drones and cars – which are many smaller batteries – individually combine to power the vehicle. Interestingly, we found that the batteries rearrange themselves when they charge and discharge, a feature not found in regular batteries.”

Peter Burke, Study Co-Author and Professor, Electrical Engineering and Computer Science, University of California-Irvine

Burke highlighted that his experiments substantiated what researchers had speculated for a considerable time while examining snapshots of preserved (non-living) mitochondria: the internal structure adapts in accordance with the metabolic demands of the cell.

A mitochondrion has the ability to generate and eliminate its “batteries” (cristae) as required. This reveals that, unlike drones and Teslas, mitochondria possess the capacity to modify their internal configurations based on the energy requirements of cells.

Burke mentioned that this research could have extensive applications in human health, including investigations into the cellular-level aging process in humans.

Burke added, “Once we understand how they create energy, we can start to think of ways to modify this for improving human health and longevity.”