The intermembrane space (IMS) is the space occurring between or involving two or more membranes. In cell biology, it is most commonly described as the region between the
inner membrane and the
outer membrane of a
mitochondrion
A mitochondrion () is an organelle found in the cell (biology), cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosine tri ...
or a
chloroplast
A chloroplast () is a type of membrane-bound organelle, organelle known as a plastid that conducts photosynthesis mostly in plant cell, plant and algae, algal cells. Chloroplasts have a high concentration of chlorophyll pigments which captur ...
. It also refers to the space between the inner and outer nuclear membranes of the
nuclear envelope
The nuclear envelope, also known as the nuclear membrane, is made up of two lipid bilayer membranes that in eukaryotic cells surround the nucleus, which encloses the genetic material.
The nuclear envelope consists of two lipid bilayer membran ...
, but is often called the perinuclear space. The IMS of mitochondria plays a crucial role in coordinating a variety of cellular activities, such as regulation of respiration and metabolic functions. Unlike the IMS of the mitochondria, the IMS of the chloroplast does not seem to have any obvious function.
Intermembrane space of mitochondria
Mitochondria are surrounded by two membranes; the inner and outer mitochondrial membranes. These two membranes allow the formation of two aqueous compartments, which are the intermembrane space (IMS) and the matrix. Channel proteins called porins in the outer membrane allow free diffusion of ions and small proteins about 5000 daltons or less into the IMS. This makes the IMS chemically equivalent to the cytosol regarding the small molecules it contains. By contrast, specific transport proteins are required to transport ions and other small molecules across the inner mitochondrial membrane into the matrix due to its impermeability.
The IMS also contains many enzymes that use the ATP moving out of the matrix to phosphorylate other nucleotides and proteins that initiate apoptosis.
Translocation
Most of proteins destined for the
mitochondrial matrix
In the mitochondrion, the matrix is the space within the inner membrane. It can also be referred as the mitochondrial fluid. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitoc ...
are synthesized as
precursors in the cytosol and are imported into the mitochondria by the translocase of the outer membrane (
TOM) and the translocase of the inner membrane (
TIM).
The IMS is involved in the mitochondrial protein translocation. The precursor proteins called small TIM
chaperones which are hexameric complexes are located in the IMS and they bind hydrophobic precursor proteins and delivery the precursors to the TIM.
Oxidative phosphorylation
The pyruvate generated by
glycolysis
Glycolysis is the metabolic pathway that converts glucose () into pyruvic acid, pyruvate and, in most organisms, occurs in the liquid part of cells (the cytosol). The Thermodynamic free energy, free energy released in this process is used to form ...
and the fatty acids produced by breakdown of fats enter the mitochondrial IMS through the
porins in the outer mitochondrial membrane.
Then they are transported across the inner mitochondrial membrane into the matrix and converted into the
acetyl CoA
Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized fo ...
to enter the
citric acid cycle
The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle (tricarboxylic acid cycle)—is a series of chemical reaction, biochemical reactions that release the energy stored in nutrients through acetyl-Co ...
.

The respiratory chain in the inner mitochondrial membrane carries out oxidative phosphorylation. Three enzyme complexes are responsible for the electron transport: NADH-ubiquinone
oxidoreductase
In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor. This group of enzymes usually ut ...
complex (
complex I
Respiratory complex I, (also known as NADH:ubiquinone oxidoreductase, Type I NADH dehydrogenase and mitochondrial complex I) is the first large protein complex of the respiratory chains of many organisms from bacteria to humans. It catalyzes th ...
), ubiquinone-
cytochrome
Cytochromes are redox-active proteins containing a heme, with a central iron (Fe) atom at its core, as a cofactor. They are involved in the electron transport chain and redox catalysis. They are classified according to the type of heme and its ...
c
oxidoreductase
In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor. This group of enzymes usually ut ...
complex (
complex III), and cytochrome c oxidase (
complex IV). The protons are pumped from the mitochondrial matrix to the IMS by these respiratory complexes. As a result, an electrochemical gradient is generated, which is combined by forces due to a H
+ gradient (pH gradient) and a voltage gradient (membrane potential). The pH in the IMS is about 0.7 unit lower than the one in the matrix and the membrane potential of the IMS side becomes more positively charged than the matrix side. This electrochemical gradient from the IMS to the matrix is used to drive the synthesis of ATP in the mitochondria.
Apoptosis
Releasing of
cytochrome c from the IMS to the cytosol activates
procaspases and triggers a
caspase cascade leading to
apoptosis
Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
.
Intermembrane space of chloroplasts

The intermembrane space (IMS) of the
chloroplast
A chloroplast () is a type of membrane-bound organelle, organelle known as a plastid that conducts photosynthesis mostly in plant cell, plant and algae, algal cells. Chloroplasts have a high concentration of chlorophyll pigments which captur ...
is exceedingly small, from 10 to 20 nm thick. Unlike the IMS of the mitochondria, the IMS of the chloroplast does not seem to have any obvious function. The translocase of the outer membrane (
TOC) and the translocase of the inner membrane (
TIC
A tic is a sudden and repetitive motor movement or vocalization that is not rhythmic and involves discrete muscle groups. Tics are typically brief and may resemble a normal behavioral characteristic or gesture.
Tics can be invisible to the obs ...
) mainly assist the translocation of chloroplast
precursor proteins Chaperone involvement in the IMS has been proposed but still remains uncertain. The eukaryotic
Hsp70
The 70 kilodalton heat shock proteins (Hsp70s or DnaK) are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms and play crucial roles in the development of can ...
, which is the heat shock protein of 70 kDa, typically localized in the cytoplasm is also found in the IMS of chloroplasts. The resulting hypothesis states that co-localization of Hsp70 is important for efficient translocation of protein precursors into and across the IMS of chloroplasts.
Intermembrane space of nuclear envelopes

The nuclear envelope is composed of two lipid bilayer membranes that are penetrated by
nuclear pore
The nuclear pore complex (NPC), is a large protein complex giving rise to the nuclear pore. A great number of nuclear pores are studded throughout the nuclear envelope that surrounds the eukaryote cell nucleus. The pores enable the nuclear tran ...
s and separated by a small intermembrane space, which is often called the perinuclear space. The perinuclear space is usually about 20-40 nm wide. The perinuclear translocation of certain proteins and enzymes were studied and results showed that perinuclear space was important for genome integrity and gene regulation.
References
{{DEFAULTSORT:Intermembrane Space
Cell anatomy