Mitochondrial cooperatives

Aug 13, 2013

Mitochondria, the organelles that supply the cell with energy, are highly dynamic and can link up to form complex tubular networks. A new study shows that this response can transiently compensate for a shortfall in energy production.

In , mitochondria produce most of the energy required for growth and proliferation, in the form of the universal unit of biological energy – ATP. Many other essential also take place in these membrane-bounded , which have their own small genomes. They also play crucial roles in cellular aging and . In textbooks, they are often depicted as bean-shaped organelles. But in recent years it has become clear that mitochondrial morphology is highly dynamic. Indeed, individual mitochondria can undergo repeated fusion to form branched tubular networks, whose form varies depending on the cell type. Mitochondria in , for example, link up to form long cables.

Cheese instead of cables

"Why mitochondria display so much variability in form and structure is one of the most exciting open questions in ," says Barbara Conradt, Professor of Cell and Developmental Biology at LMU. Together with postdoc Stéphane Rolland and other members of her group, Conradt is trying to understand the functional significance of the morphological diversity of mitochondria. The team uses the nematode Caenorhabditis elegans as a , and their latest work focuses on a mutant in which muscle mitochondria fail to form the typical cables, owing to the partial inactivation of the nuclear gene mma-1. "Instead of linking up into well-defined cables, the mitochondria in the mutant overdo it, and undergo hyperfusion to form a large structure that looks rather like a chunk of Swiss cheese," says Conradt.

Loss of mma-1 also impairs the function of a protein complex involved in the synthesis of ATP in the mitochondria. Nevertheless, the researchers found, much to their surprise that mutant cells produce about the same amount of ATP as normal cells, despite making only half as much of the protein product encoded by the mma-1 gene. "We concluded from this that hyperfusion enhances the efficiency of ATP synthesis," says Conradt. This idea is supported by the finding that inhibition of hyperfusion renders the mma-1 mutant inviable.

Mitochondria and neurodegeneration

In collaboration with Konstanze Winklhofer, Conradt and her coworkers found the same hyperfusion phenotype in mammalian cells in which the mma-1 homolog, the gene LRPPRC, was partially inactivated. As in C. elegans, hyperfusion can transiently compensate for defects in ATP production. A few days after gene inactivation, energy production collapses in the . "This is the first time that hyperfusion has been shown to represent an attempt to counteract the effects of a genetic defect in mitochondrial energy production. It probably works for only a limited time because the mutation involved also has an adverse impact on other mitochondrial functions," Conradt suggests.

Interestingly, mutations in the mammalian LRPPRC are associated with one form of Leigh syndrome, a serious neurodegenerative disorder that is characterized by a perturbation in mitochondrial energy metabolism. "So our findings are clearly of medical relevance, and could lead to new insights into this disease, as our C. elegans mutant provides an excellent experimental model for the study of its pathogenesis," says Conradt. She and her team will now test whether stimulating mitochondrial ATP production will reverse the hyperfusion phenotype. If sufficient numbers of functional mitochondria could be recovered in this way, the organism could perhaps compensate for defects in mma-1/LRPPRC in the long term.

Explore further: Novel drug acts in unique way to protect against kidney injury

More information: PNAS 2013. www.pnas.org/content/early/2013/07/17/1303872110.abstract

add to favorites email to friend print save as pdf

Related Stories

Nuts and Bolts: Mitochondria

Mar 27, 2012

Hailed as the ‘powerhouses’ of the cell in thousands of textbooks, mitochondria rightly have a reputation as essential pieces of cellular machinery. Find out more with this quick guide by Chrissie ...

Surviving fasting in the cold

Jul 02, 2013

King penguin chicks survive harsh winters with almost no food by minimising the cost of energy production. A new study, to be presented at the Society for Experimental Biology meeting in Valencia on the 3rd ...

Recommended for you

For resetting circadian rhythms, neural cooperation is key

16 hours ago

Fruit flies are pretty predictable when it comes to scheduling their days, with peaks of activity at dawn and dusk and rest times in between. Now, researchers reporting in the Cell Press journal Cell Reports on April 17th h ...

Rapid and accurate mRNA detection in plant tissues

18 hours ago

Gene expression is the process whereby the genetic information of DNA is used to manufacture functional products, such as proteins, which have numerous different functions in living organisms. Messenger RNA (mRNA) serves ...

For cells, internal stress leads to unique shapes

Apr 16, 2014

From far away, the top of a leaf looks like one seamless surface; however, up close, that smooth exterior is actually made up of a patchwork of cells in a variety of shapes and sizes. Interested in how these ...

User comments : 0

More news stories

Scientists tether lionfish to Cayman reefs

Research done by U.S. scientists in the Cayman Islands suggests that native predators can be trained to gobble up invasive lionfish that colonize regional reefs and voraciously prey on juvenile marine creatures.

Deadly human pathogen Cryptococcus fully sequenced

Within each strand of DNA lies the blueprint for building an organism, along with the keys to its evolution and survival. These genetic instructions can give valuable insight into why pathogens like Cryptococcus ne ...

Biologists help solve fungi mysteries

(Phys.org) —A new genetic analysis revealing the previously unknown biodiversity and distribution of thousands of fungi in North America might also reveal a previously underappreciated contributor to climate ...

Leeches help save woman's ear after pit bull mauling

(HealthDay)—A pit bull attack in July 2013 left a 19-year-old woman with her left ear ripped from her head, leaving an open wound. After preserving the ear, the surgical team started with a reconnection ...

Venture investments jump to $9.5B in 1Q

Funding for U.S. startup companies soared 57 percent in the first quarter to a level not seen since 2001, as venture capitalists piled more money into an increasing number of deals, according to a report due out Friday.