It is well known that mitochondria play crucial roles in the life and death of cells. These mighty organelles power biochemical reactions in the cell by producing ATP. Without them, we would not be able to function as organisms. Somewhat paradoxically, mitochondria also act as the grim reaper – deciding which cells die as they age and deteriorate.
Remarkably, although mitochondria are commonly studied in labs from middle school to major universities, we are still learning about them. Research from the Ruohola-Baker Lab, published this week in the journal Stem Cell Reports, now shows that mitochondria also determine whether a stem cell can reproduce or not, a finding that sheds new light on the factors that influence cell cycles.
In the study, investigators led by ISCRM Associate Director Hannele Ruohola-Baker, PhD, explored the mechanisms by which normal and cancerous stem cells undergo cell-cycle arrest to avoid overgrowth or apoptosis, the protective, reversible quiescence that can allow tumorous cells to survive chemotherapy and other cancer treatments.
The researchers show that, surprisingly, mitophagy (the degradation of mitochondria) is necessary for reversible quiescence in both Drosophila and human iPSC stem cell models – and reveal a potential new approach to controlling this process for therapeutic purposes.
Mindful that imprecise control of mitochondria can be harmful, the researchers focused on the Pink/Parkin signaling pathway, which when mutated can cause defective mitophagy and contribute to Parkinson’s disease. The team discovered that a key cell cycle regulator, CyclinE, on the mitochondrial outer membrane is the target for Parkinson’s disease genes in stem cells (purple Fig.1), suggesting a novel mitochondrial checkpoint for cell cycle.
In a related review published in Cells, investigators from the Ruohola-Baker Lab discuss the molecular mechanisms of embryonic diapause (the reproductive strategy and state of suspended development occurs in over 130 mammals) and examine recent studies that have revealed critical regulators of diapause, a quiescence used by normal stem cells and diapause-like quiescence used by cancers. The first author of the review is Asis Hussein, PhD, a postdoctoral researcher in the lab.
The first authors of the study are Tommy Taslim, Abdiasis Hussein, Riya Keshri and Julien Ishibashi from the Ruohola-Baker Lab. The project was powered by 12 undergraduate students who worked in the study as their final undergraduate project. ISCRM faculty member Julie Mathieu, PhD is also an author of both the study and the review.