an-improved-method-to-isolate-mitochondrial-contact-sites

An Improved Method to Isolate Mitochondrial Contact Sites

Mitochondria are present in virtually all eukaryotic cells and perform essential functions that go far beyond energy production, for instance, the ...

Ludwig-Maximilians University Munich

Mitochondria perform a plethora of functions in various cells of different tissues. Their architecture differs remarkably, for instance in neurons versus steroidogenic cells. Furthermore, aberrant mitochondrial architecture results in mitochondrial dysfunction. This indicates strongly that mitochondrial architecture and function are intimately linked. Therefore, a deep knowledge about the determinants of mitochondrial architecture and their function on a molecular level is of utmost importance. In the past decades, various proteins and protein complexes essential for formation of mitochondrial architecture have been identified. Here we will review the current knowledge of the MICOS complex, one of the major structural elements of mitochondria. MICOS is a multi-subunit complex present in the inner mitochondrial membrane. Multiple interaction partners in the inner and outer mitochondrial membrane point to participation in a multitude of important processes, such as generation of mitochondrial architecture, lipid metabolism, and protein import into mitochondria. Since the MICOS complex is highly conserved in form and function throughout evolution, we will highlight the importance of MICOS for mammals. We will emphasize in particular the current knowledge of the association of MICOS with severe human diseases, including Charcot-Marie-Tooth disease type 2, Alzheimer's disease, Parkinson's disease, Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

The MICOS complex, a structural element of mitochondria with versatile functions.

Mitochondria are essential organelles of eukaryotic cells and are characterized by their unique and complex membrane system. They are confined from the cytosol by an envelope consisting of two membranes. Signals, metabolites, proteins and lipids have to be transferred across these membranes via proteinaceous contact sites to keep mitochondria functional. In the present study, we identified a novel mitochondrial contact site in Saccharomyces cerevisiae that is formed by the inner membrane protein Cqd1 and the outer membrane proteins Por1 and Om14. Similar to what is found for the mitochondrial porin Por1, Cqd1 is highly conserved, suggesting that this complex is conserved in form and function from yeast to human. Cqd1 is a member of the UbiB protein kinase-like family (also called aarF domain-containing kinases). It was recently shown that Cqd1, in cooperation with Cqd2, controls the cellular distribution of coenzyme Q by a yet unknown mechanism. Our data suggest that Cqd1 is additionally involved in phospholipid homeostasis. Moreover, overexpression of CQD1 and CQD2 causes tethering of mitochondria to the endoplasmic reticulum, which might explain the ability of Cqd2 to rescue ERMES deletion phenotypes.

Max E. Harner

Department of Cell Biology,
Biomedical Center,
Medical Faculty,
Department of Cell Biology, Biomedical Center, Medical Faculty

Ludwig-Maximilians University Munich

An Improved Method to Isolate Mitochondrial Contact Sites

Max E. Harner

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Cell Biology,Biomedical Center,Medical Faculty,Department of Cell Biology, Biomedical Center, Medical Faculty

Ludwig-Maximilians University Munich

An Improved Method to Isolate Mitochondrial Contact Sites

Department of Cell Biology,
Biomedical Center,
Medical Faculty,
Department of Cell Biology, Biomedical Center, Medical Faculty