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Review
. 2015 May:22:96-118.
doi: 10.1016/j.mito.2015.01.008. Epub 2015 Jan 29.

Mitochondrial Diseases Part II: Mouse models of OXPHOS deficiencies caused by defects in regulatory factors and other components required for mitochondrial function

Luisa Iommarini  1 , Susana Peralta  2 , Alessandra Torraco  3 , Francisca Diaz  4
Affiliations
Review

Mitochondrial Diseases Part II: Mouse models of OXPHOS deficiencies caused by defects in regulatory factors and other components required for mitochondrial function

Luisa Iommarini et al. Mitochondrion. 2015 May.

Abstract

Mitochondrial disorders are defined as defects that affect the oxidative phosphorylation system (OXPHOS). They are characterized by a heterogeneous array of clinical presentations due in part to a wide variety of factors required for proper function of the components of the OXPHOS system. There is no cure for these disorders owing to our poor knowledge of the pathogenic mechanisms of disease. To understand the mechanisms of human disease numerous mouse models have been developed in recent years. Here we summarize the features of several mouse models of mitochondrial diseases directly related to those factors affecting mtDNA maintenance, replication, transcription, translation as well as other proteins that are involved in mitochondrial dynamics and quality control which affect mitochondrial OXPHOS function without being intrinsic components of the system. We discuss how these models have contributed to our understanding of mitochondrial diseases and their pathogenic mechanisms.

Keywords: Mitochondrial DNA; Mitochondrial diseases; Mitochondrial dynamics; Mitochondrial transcription; Mouse models; Quality control.

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Conflict of interest statement

Conflict of interest statement: Authors have nothing to declare.

Figures

Figure 1
Figure 1. Mouse models of mitochondrial diseases
Mouse models that affect the oxidative phosphorylation system which is represented in light yellow in the mitochondrial inner membrane. Mouse models affecting mitochondrial dynamics are represented in light orange (MFN1, MFN2, OPA1 and DRP1). Mouse models of proteins involved in mtDNA replication, transcription and translation are represented in light pink (POLG, POLG2, TFAM, TFB1, TWINKLE, MTERFs and LRPPRC). Mouse models of proteins required for dNTPs synthesis, and mtDNA synthesis and stability are represented in light blue (RRM2B, TK2, TP, UP and MPV17). Mouse model for mtDNA deletion/depletion caused by double-strand brakes (red bolt) is represented in red (mito-Pst1). Mouse models of protein quality control are represented in blue (CLPP, PHB, PARL, OMI, OMA1, AFG3L2+SPG7, AFG3L2). Other mouse models (AIF1, ANT1 and FXN). NDPs: nucleotide diphosphates; dNDPs: deoxy-NDPs; dNTPs: deoxy nucleotide triphosphates; Pyr: pyrimidines; mtDNA: mitochondrial DNA.
See this image and copyright information in PMC

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