Monday, 3 November 2014

A Mitofusin-2 – dependent inactivating cleavage of Opa1 links changes in mitochondria cristae and ER contacts in the postprandial liver

Aditi Sood,Danny Vijey Jeyaraju, Julien Prudent, Alexandre Caron, Philippe Lemieux, Heidi May McBride, Mathieu Laplante, Katalin Tóth, and Luca Pellegrini; PNAS

In this paper, they study the liver of two groups of mice: 1) the first group was killed 2 hours after feeding 2) the second group was killed 5h after feeding. Nutrient levels become limited in the 5h group, they then studied the shape of cristae and the amount of ER-mitochondria contact in the 5h group as compared to the 2h group.

Changes in cristae structure

The number of cristae per mitochondrion had decreased in liver cells with limited nutrients. The average length per cristae remained the same.


Changes in mitochondria-ER contact
About 1 in 4 mitochondria in both groups was in contact with the ER, but in the nutrient limiting group the mitochondrial surface area in contact with the ER had increased. The ER thus wrapped more extensively around mitochondria when nutrients were limited.

OPA1 cleavage observed which is MFN2 dependent

They then continue to investigate what caused the cristae remodelling.
Total OPA1 expression levels were the same in both groups, but two new forms of OPA1 were identified in nutrient-limiting conditions. These two forms were the result of OPA-1 cleavage by an unknown cysteine protease.The sites of cleavage were named C1 and C2. Cleavage at either C1 or C2 is likely to inactive the dynamin-like activity of OPA1, but does not interfere with mitochondrial dynamics. Mfn2 was required for the observed OPA1 cleavage, further suggesting a link between changes in cristae shape and changes in mitochondria-ER contact (because MFN2 is involved in mitochondria-ER tethering).


 Mitochondria adapt to changes in nutrient availability by remodelling their cristae and changing the amount of mitochondria-ER contact. The cristae remodelling is mediated through MFN2-dependent OPA1 cleavage by a cysteine protease. The study suggests that cristae remodelling and changes in mitochondria-ER contact are coupled during nutrient depletion.

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