How do peroxisomes interact with other organelles

Molecular basis for organelle contact zone deciphered

Scientists from the Medical Faculty Mannheim at the University of Heidelberg and the University of Exeter were able to demonstrate how intracellular organelles connect with one another via defined contact zones and exchange metabolites and signals in the process. The results obtained within the framework of a cooperation project between the research team led by PD Dr. Markus Islinger from the neuroanatomy department of the Medical Faculty Mannheim and the group of Prof. Dr. Michael Schrader at the University of Exeter, UK, are currently published in the Journal of Cell Biology (JCB). A new class of organelle-specific diseases can evidently be defined through knowledge of the molecular structure of the contact zones of organelles.

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Intracellular organelles such as mitochondria, peroxisomes or the endoplasmic reticulum are small, self-contained functional units within the cell that perform specific tasks in cell metabolism. Current scientific findings show that the organelles enclosed by membranes are not present as isolated units in the cell, but rather connect with one another via defined contact zones.

Where do the mitochondria, the “power plants” of our cells, come from? Originally, they were hydrogen-producing bacteria that were enclosed by other primordial cells. The primordial cells needed hydrogen for their own metabolism.

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Molecular components previously unknown

Such contact zones between peroxisomes and the endoplasmic reticulum (ER) were already observed with an electron microscope in mammals more than 50 years ago. However, the molecular components that mediate this interaction were previously unknown. Both peroxisomes and the ER are essential for the smooth running of human lipid metabolism.

Identified two proteins

The scientists identified two proteins that are responsible for the formation of the contact zones between peroxisomes and the ER: The peroxisomal membrane protein ACBD5 and the ER protein VAPB form a protein complex that attaches both organelles to one another. The first results show that the contact formed is responsible for the transfer of lipids between the two organelles.

New genus of diseases?

A defect in the genes responsible for lipid metabolism leads to life-threatening hereditary diseases. Recently, research groups from the Netherlands and Saudi Arabia described patients with genetic defects in ACBD5 that lead to irreversible damage to the brain and retina. The basis of the disease process of this ACBD5 deficiency could be a disruption of communication between ER and peroxisomes and thus represent an example of a new genus of organelle-specific diseases (see accompanying Spotlight article in JCB by Maya Schuldiner at).

Significance for human health

PD Dr. Islinger in Mannheim to get to the bottom of things. To do this, he uses a mouse line that has a defect in the ACBD5 gene and can therefore no longer produce the protein. The researchers hope that further studies on this so-called knockout mouse will provide detailed knowledge about the pathology of ACBD5 deficiency and thus general information on the importance of organelle contact zones for human health. (idw, red)