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Review
. 2019 Sep 3;20(17):4311.
doi: 10.3390/ijms20174311.

Functional Interplay Between Cristae Biogenesis, Mitochondrial Dynamics and Mitochondrial DNA Integrity

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Free PMC article
Review

Functional Interplay Between Cristae Biogenesis, Mitochondrial Dynamics and Mitochondrial DNA Integrity

Arun Kumar Kondadi et al. Int J Mol Sci. .
Free PMC article

Abstract

Mitochondria are vital cellular organelles involved in a plethora of cellular processes such as energy conversion, calcium homeostasis, heme biogenesis, regulation of apoptosis and ROS reactive oxygen species (ROS) production. Although they are frequently depicted as static bean-shaped structures, our view has markedly changed over the past few decades as many studies have revealed a remarkable dynamicity of mitochondrial shapes and sizes both at the cellular and intra-mitochondrial levels. Aberrant changes in mitochondrial dynamics and cristae structure are associated with ageing and numerous human diseases (e.g., cancer, diabetes, various neurodegenerative diseases, types of neuro- and myopathies). Another unique feature of mitochondria is that they harbor their own genome, the mitochondrial DNA (mtDNA). MtDNA exists in several hundreds to thousands of copies per cell and is arranged and packaged in the mitochondrial matrix in structures termed mt-nucleoids. Many human diseases are mechanistically linked to mitochondrial dysfunction and alteration of the number and/or the integrity of mtDNA. In particular, several recent studies identified remarkable and partly unexpected links between mitochondrial structure, fusion and fission dynamics, and mtDNA. In this review, we will provide an overview about these recent insights and aim to clarify how mitochondrial dynamics, cristae ultrastructure and mtDNA structure influence each other and determine mitochondrial functions.

Keywords: cristae; fusion and fission; mitochondrial dynamics; mitochondriopathy; mtDNA.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Functional interplay of mitochondrial dynamics, cristae biogenesis and mtDNA integrity: The scheme describes that the balance between mitochondrial dynamics, cristae biogenesis and mtDNA structure helps to manage integrity and function of mitochondrial DNA. Mitochondrial dynamics comprising fission and fusion cycles helps in redistribution and complementation of mtDNA within mitochondria. Lack of fusion causes subsequent loss of mtDNA from the fragmented mitochondria, whereas accumulation of aggregated nucleoids is observed in elongated mitochondria generated during a fission defect. Relationship between mitochondrial dynamics and cristae biogenesis and mtDNA organization is evident by several examples where the loss of fusion or fission concurrently shows defective cristae and mtDNA loss. Altered morphology of mitochondria is observed with mtDNA aberrations during cristae biogenesis defects. The internal mitochondrial structure is modulated by the following key players regulating cristae shape: OPA1 oligomers, MICOS, and F1Fo ATPase synthase. Chronic loss of OPA1 is accompanied by cristae defects as well as mtDNA loss. Depletion of MIC60 results in loss of CJs together with accumulation of enlarged nucleoids. The function and organization of mtDNA nucleoids is schematically depicted. On average, 1.4 mtDNA molecules are present per nucleoid which also contains associated proteins required for compaction, replication and transcription. ETC, electron transport chain (complex II is not shown).

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