Mitochondrial compartmentalization: emerging themes in structure and function

Trends Biochem Sci. 2021 Nov;46(11):902-917. doi: 10.1016/j.tibs.2021.06.003. Epub 2021 Jul 7.


Within cellular structures, compartmentalization is the concept of spatial segregation of macromolecules, metabolites, and biochemical pathways. Therefore, this concept bridges organellar structure and function. Mitochondria are morphologically complex, partitioned into several subcompartments by a topologically elaborate two-membrane system. They are also dynamically polymorphic, undergoing morphogenesis events with an extent and frequency that is only now being appreciated. Thus, mitochondrial compartmentalization is something that must be considered both spatially and temporally. Here, we review new developments in how mitochondrial structure is established and regulated, the factors that underpin the distribution of lipids and proteins, and how they spatially demarcate locations of myriad mitochondrial processes. Consistent with its pre-eminence, disturbed mitochondrial compartmentalization contributes to the dysfunction associated with heritable and aging-related diseases.

Keywords: bioenergetics; cristae; macromolecular trafficking; mitochondria; morphogenesis; ultrastructure.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Mitochondria* / metabolism
  • Mitochondrial Membranes* / metabolism
  • Mitochondrial Proteins / metabolism


  • Mitochondrial Proteins