Less than perfect divorces: dysregulated mitochondrial fission and neurodegeneration.

Abstract:

:Research efforts during the last decade have deciphered the basic molecular mechanisms governing mitochondrial fusion and fission. We now know that in mammalian cells mitochondrial fission is mediated by the large GTPase dynamin-related protein 1 (Drp1) acting in concert with outer mitochondrial membrane (OMM) proteins such as Fis1, Mff, and Mief1. It is also generally accepted that organelle fusion depends on the action of three large GTPases: mitofusins (Mfn1, Mfn2) mediating membrane fusion on the OMM level, and Opa1 which is essential for inner mitochondrial membrane fusion. Significantly, mutations in Drp1, Mfn2, and Opa1 have causally been linked to neurodegenerative conditions. Despite this knowledge, crucial questions such as to how fission of the inner and outer mitochondrial membranes are coordinated and how these processes are integrated into basic physiological processes such as apoptosis and autophagy remain to be answered in detail. In this review, we will focus on what is currently known about the mechanism of mitochondrial fission and explore the pathophysiological consequences of dysregulated organelle fission with a special focus on neurodegenerative conditions, including Alzheimer's, Huntington's and Parkinson's disease, as well as ischemic brain damage.

journal_name

Acta Neuropathol

journal_title

Acta neuropathologica

authors

Oettinghaus B,Licci M,Scorrano L,Frank S

doi

10.1007/s00401-011-0930-z

subject

Has Abstract

pub_date

2012-02-01 00:00:00

pages

189-203

issue

2

eissn

0001-6322

issn

1432-0533

journal_volume

123

pub_type

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