Journal Club

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Journal Club: Newfound avenue for disrupting peroxisome organelles could have big implications in the cell

Researchers unexpectedly found that a protein seen in mitochondria can also influence peroxisome formation, potentially having big implications for cell activity. Image credit: Shutterstock/Wire_man

Researchers unexpectedly found that a protein seen in mitochondria (illustrated above) can influence peroxisome formation.       Image credit: Shutterstock/Wire_man

Peroxisomes are packages of enzymes that help destroy toxins and digest fuels for cells. Disrupt the assembly of these organelles, and the results could be fatal for humans. Previously, all mutant proteins linked to such disorders were thought to be based only in peroxisomes themselves. Now scientists unexpectedly find that a protein seen in mitochondria can also influence peroxisome formation, findings published Feb. 7 in the Journal of Cell Biology.

Nearly all eukaryotes, organisms with cell nuclei, contain peroxisomes. The dozens of enzymes these organelles contain play a variety of roles, from neutralizing toxins such as alcohol and hydrogen peroxide to digesting fatty acids to help provide energy to cells.

While investigating peroxisome-deficient cells from Chinese hamsters, study senior author Yukio Fujiki, a molecular cell biologist at Kyushu University in Fukuoka, Japan, and his colleagues discovered that the mutation responsible for the hamsters’ condition was not linked to any known peroxisome formation disorder. Further, they found, to their surprise, that the gene linked to this mutation encoded a protein known as VDAC2, which is found in the membranes of mitochondria, the powerhouses of eukaryotic cells. The absence of this protein led to a severe lack of peroxisomes.

Previous research found that VDAC2 keeps a protein known as BAK inactive on mitochondria. BAK is known to promote apoptosis (a form of cell death) by disrupting the mitochondria — specifically, by rendering their outer membranes porous. But with VDAC2 absent, BAK appears to shift from the mitochondria to peroxisomes, where it makes their membranes porous, causing them to leak proteins such as catalase.

Fujiki notes that when BAK is active on mitochondria, it can prove lethal to cells, triggering apoptosis when the cells are threatened by reactive oxygen species. In contrast, active BAK on peroxisomes could help save cells by releasing catalase, an enzyme that can eliminate reactive oxygen species in the cell. “The completely opposite functions of BAK depend on its organelle localization,” Fujiki explains.

The peroxisome role in apoptosis could potentially have manifold implications. Past research has suggested that insights into apoptosis could elucidate aging, and possibly provide an avenue for fighting cancer by triggering self-destruction in tumor cells. “These findings lead one to wonder if peroxisomes might play a role in apoptosis,” says Richard Rachubinski, chair of cell biology at the University of Alberta in Edmonton, Canada, who did not take part in this research. “That’s an avenue that I don’t think has ever been investigated at all.”

“More and more, we’re seeing interplay between organelles,” Rachubinski adds, noting other recent work published in Journal of Cell Biology, which reported that the endoplasmic reticulum also communicates with peroxisomes. “It makes sense that the whole cell has organized responses to its environment, and maybe apoptosis is an area where organelles have to communicate with each other.”

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