Mitochondria: Structure and Role in Respiration


Mitochondria are eukaryotic organelles of endosymbiotic origin, which conserve their own genome and gene expression machinery. They are highly dynamics organelles and form an elaborated network in the cell cytosol. Mitochondria fulfil various important roles in cellular metabolism. They are commonly known as ‘the powerhouse of the cell’ for their pivotal role in the conversion of nutrient‐derived energy in the form of ATP molecules, through the mitochondria‐housed pathways of citric acid cycle and oxidative phosphorylation. Besides, much broader is the role that these organelles play in cellular metabolism and survival. Mitochondria fulfil important roles in the biosynthesis of essential molecules, such as lipids, amino acids, haem and iron–sulphur cluster, and are a major cellular site of reactive oxygen species production. Moreover, mitochondrial dysfunction is the cause of devastating human encephalomyopathies and it has been linked with neurodegeneration, cancer and ageing.

Key Concepts

  • Mitochondria are semi‐autonomous organelles that are descendants of endosymbiotic bacteria.
  • Mitochondria play a pivotal role in cellular energy production through the mitochondria‐housed pathways of citric acid cycle, fatty acid oxidation, respiration and oxidative phosphorylation (OXPHOS).
  • Mitochondria have an important anabolic role in cellular metabolism, as they are fundamental for the synthesis of several amino acids, nucleobases and enzymatic cofactors such as haem and Fe‐S clusters.
  • Mitochondria are membrane‐bound organelles. They have two distinct membranes: the outer and the inner membrane. The inner membrane is highly impermeable to ions and forms an extensive series of invaginations called cristae.
  • In the cell, mitochondria form a continuous and highly dynamic network. In addition, they intimately interact with other cellular structures, such as the cytoskeleton and the endoplasmic reticulum.
  • Mitochondria retain their own hereditary material, the mitochondrial DNA (mtDNA), and their own translation apparatus or mitoribosomes.
  • mtDNA is present in ∼1000–10 000 copies per cell and encodes for a handful of proteins, all subunits of the OXPHOS system.
  • The OXPHOS system is located in the mitochondrial cristae and is formed by the mitochondrial respiratory chain (MRC) and the ATP synthase or complex V. The MRC is formed by four multimeric complexes (complex I–IV) and two mobile electron carriers, coenzyme Q and cytochrome c. In addition, MRC complexes interact to form organised supra‐structures called supercomplexes or respirasomes.
  • The assembly of the OXPHOS complexes is a complicated and highly regulated process requiring a large number of ancillary factors.
  • In humans, defects of the OXPHOS system are associated with devastating diseases, known as mitochondrial disorders, which are multisystemic, although mainly affecting highly energy‐demanding tissues such as brain, heart and muscle.

Keywords: chemiosmotic theory; oxidative phosphorylation; citric acid cycle; ATP; mitochondrial respiratory chain; endosymbiotic theory; mitochondrial biogenesis

Figure 1. Mitochondrial architecture. (a) Schematic representation of mitochondrial ultrastructure. (b) Confocal microscopy image of a human fibroblast cell in which the mitochondrial network is visualised with the fluorescent dye Mitotraker Red.
Figure 2. Mitochondrial biogenesis. (a) Schematic representation of the human mitochondrial DNA. Protein‐encoding and rRNA genes are depicted in green and blue, respectively. tRNAs are identified by a black mark and the one letter amino acid code. OH and OL indicate the origins of replication of the heavy and light strand, respectively. LSP, HSP1 and HSP2 identified the three transcriptional promoters. The areas covered by each polycistronic transcripts are indicated by a black arrow. (b) Cartoon depicting the major mitochondrial protein import systems as described in the text. TOM (translocase of the outer membrane complex), SAM (sorting and assembly machinery), TIMs (small TIM chaperones), TIM22 (translocase of the inner membrane 22 complex), TIM23 (translocase of the inner membrane 23 complex), PAM (presequence translocase‐associated motor).
Figure 3. Oxidative phosphorylation system. As electrons (derived from NADH or FADH2) are transported (red line) down the electron transport chain (formed by complexes I to IV and two mobile electron carriers, ubiquinol (QH2) and cytochrome c) until the final electron acceptor, molecular oxygen, protons are being pumped from the matrix to the cytosolic side of the inner mitochondrial membrane, thus establishing a proton gradient. This gradient is used by the ATP synthase to generate ATP.
Figure 4. Physical organisation of the mitochondrial respiratory chain. (a) Schematic representation of mammalian MRC complexes and supercomplexes. Complex II is not represented. (b) Visualisation by Blue‐Native electrophoresis of the MRC complexes and supercomplexes present in mammalian mitochondria. Complex II is not shown.
Figure 5. Integration of cytosolic and mitochondrial pathways. The citric acid cycle has integrative functions in a complex network of cellular biosynthetic and degradative processes. A cell may derive energy (in the form of ATP) from different carbon sources including carbohydrates, amino acids (proteins) and lipids. Conversely, breakdown products and intermediates of oxidative metabolism may be used for biosynthetic pathways.


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Further Reading

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Fontanesi, Flavia(May 2015) Mitochondria: Structure and Role in Respiration. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001380.pub2]