Insight & Intelligence

More »

GEN News Highlights

More »
April 16, 2018

Mitochondria Choked with Proteins Can Activate Gag Reflex

Source: wir0man/Getty Images

  • When the cell tries to stuff too many proteins into its mitochondria, protein blockages and backups may result—obstructions for which no cell-level version of the Heimlich maneuver is available. Instead of putting a physical squeeze on its energy-producing organelles, the cell resorts to another mechanism—mitoCPR, or the mitochondrial compromised protein import response.

    To discover mitoCPR, scientists based at the Massachusetts Institute of Technology induced excessive expression of nuclear-encoded mitochondrial proteins within yeast cells. Essentially, the scientists, Hilla Weidberg, Ph.D., and Angelika Amon, Ph.D., encouraged cells to treat their mitochondria like force-fed geese. Then the scientists observed the results.

    Upon mitochondrial import stress, cells mounted the mitoCPR response. This response begins with the expression of PDR3, which in turn increases expression of two additional genes that facilitate the clearing of excess proteins.

    Additional details about mitoCPR appeared April 13 in the journal Science, in an article entitled “MitoCPR—A Surveillance Pathway That Protects Mitochondria in Response to Protein Import Stress.”

    “[MitoCPR] is activated when mitochondrial import is stalled in order to induce the removal of mitochondrial proteins accumulating on the mitochondrial surface,” the article’s authors noted. “Clearance of precursors is critical for maintaining mitochondrial functions during import stress. We propose that mitoCPR could be especially important when the import machinery is overwhelmed, as may occur in situations that require the rapid expansion of the mitochondrial compartment.”

    Mitochondria are essential organelles that play a critical role in supporting cell health, producing energy and sustaining many essential biological molecules, such as iron sulfur clusters and heme. However, despite retaining their own DNA, mitochondria must still import many proteins encoded by the cell's nuclear DNA from the surrounding cytoplasm.

    Until the current study, it was unclear how mitochondria cope when their import machinery is overwhelmed with a high volume of proteins or perhaps damaged proteins.

    “Our results also shed light on the mechanism by which mitoCPR protected mitochondria,” the authors of the current study detailed. “Upon mitochondrial import stress, Pdr3 induced expression of Cis1." "Coimmunoprecipitation analyses showed that Cis1 recruited the AAA+ adenosine triphosphatase Msp1 to the translocase by binding to the translocase receptor Tom70. There, the two proteins mediated the clearance and proteasomal degradation of proteins that failed to be imported into mitochondria.”

    Whether a mitochondrial import stress response exists in higher eukaryotes, like humans, remains to be determined, the scientists indicated.

Related content