This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Mitochondria are the tiny powerpacks that supply most of the energy our cells need. Their ability to generate this energy relies on a distinctive architecture: two membranes, one tucked inside the other, separated by a narrow gap called the intermembrane space (IMS).
This tiny space helps sustain the chemistry of energy production, making its organization critical to how these cellular powerpacks function. Now, a new study led by a University of Ottawa Faculty of Medicine investigator reports a discovery: the volume of the IMS is genetically controlled and adjustable. By controlling where this space expands or narrows within each mitochondrion, cells can actively shape the internal architecture of their powerpacks and tune how they function.
Published in Science Advances, the study identifies SPRIZ—short for 'SPatial Regulator of the mitochondrial Intermembrane Zone'—as a key protein that cells use to shape the internal architecture of their powerpacks. Its discovery opens a new path to understanding how disruptions in this delicate spacing may contribute to diseases in which mitochondria fail to meet cells' energy needs, or in which damaged powerpacks are not properly maintained or cleared away, as occurs in Parkinson's disease. Working with collaborators at uOttawa and in the United States, the team combined computer simulations of molecular movement, genetics, large-scale protein analysis and advanced imaging, including three-dimensional electron tomography.
Together, these approaches showed how SPRIZ bridges the two mitochondrial membranes, forming a molecular pillar that holds open the space between them. This ability to connect the membranes while keeping them apart is what makes SPRIZ distinctive, explains Dr. Luca Pellegrini, a full professor in the faculty's Department of Biochemistry, Microbiology and Immunology who led the study.
While many membrane tethers bring membranes close enough to exchange materials, SPRIZ appears to use that connection to maintain a defined spacing. "What makes SPRIZ so unexpected is that it uses a familiar mechanism—a tether—to do something different: it connects the two mitochondrial membranes while acting as a rigid pillar that holds them a set distance apart, so the room between them keeps a defined height," Pellegrini explains. The team put this molecular spacing system to the test: altering it in laboratory experiments substantially changed the size of the IMS.
Like adjusting the height of a ceiling, changing these molecular supports reshaped the room within. The findings show that cells have genetic instructions for setting the dimensions of this essential space, giving them control over the internal layout of their powerpacks. Even a tiny change in the room between mitochondrial membranes can change what happens inside it.
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