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Bioenergetics  ·  Article

Mitochondrial dynamics (fission, fusion and mitophagy)

Dynamin-related GTPases drive the process. Fusion joins the outer and inner membranes in two steps.5 Division depends on a ring of DRP1 around the organelle.3 Reviewers link these events to quality control, because division or loss of fusion proteins can lead to removal of damaged organelles.8

Earliest held
2017, Carreras-Sureda A, Pihán P…
Most discussed in
Mitochondrial Bioenergetics and Dynamics in…, 2020
In the library
24 passages in 6 works
Rewritten
2026-10-04
18501875190019251950197520002025Carreras-Sureda A, Pihán P, Hetz C, 20171Martínez J, Marmisolle I, Tarallo D…, 20202Martínez J, Marmisolle I, Tarallo D…, 20203Martínez J, Marmisolle I, Tarallo D…, 20204Protasoni M, Zeviani M, 20215Protasoni M, Zeviani M, 20216Urra FA, Fuentes-Retamal S, Palominos…, 20217Cioffi F, Giacco A, Goglia F, Silvestri…, 20228Iorio R, Petricca S, Mattei V, Delle…, 20249
01

Fusion machinery

Martínez and colleagues (2020) list OPA1, MFN1 and MFN2 as the proteins of mitochondrial fusion. They describe a long OPA1 form in the inner membrane that promotes fusion of that membrane, and a short soluble form in the intermembrane space that maintains cristae structure.2 Protasoni and Zeviani (2021) present fusion as a two-step mechanism, with mitofusins acting on the outer membrane and OPA1 on the inner membrane.5 They add that OPA1 has been shown to be the sole regulator of cristae width and of junction diameter and number.6 Carreras-Sureda and colleagues (2017) note that MFN2 also takes part in ER–mitochondria contacts. They state that whether it acts there as a tether or a spacer is still debated.1

02

Fission and its partners

Martínez and colleagues describe fission as the work of DRP1. This cytosolic GTPase is recruited to the outer membrane by receptor proteins, and it forms a ring-like structure that constricts the organelle.3 The same authors report that contacts with the endoplasmic reticulum determine where fission events occur.4 They also list actin, myosin II, septin 2, the ER protein inverted formin 2 and a mitochondrial Spire1 isoform as required components of fission.3 They state that fusion and fission are both highly regulated, through protein levels, GTPase activity and post-translational modification.3

03

Quality control and disease

Cioffi and colleagues (2022) describe mitochondrial dynamics and autophagy as collaborating parts of one quality control system. In their account, division or loss of Mfn2 or OPA1 can remove damaged organelles from the network and allow mitophagy.8 Urra and colleagues (2021) report that stiff extracellular matrix promotes fusion through β1-integrin and kindlin-2 signaling.7 They also report that soft matrix raises DRP1 expression and fission and reduces cancer cell spreading. DRP1 knockdown blocked the fission but not the change in spreading, so they suggest other components take part.7 Iorio and colleagues (2024) cite work in which increased fission and mitochondrial DNA damage precede cell death in diabetic retinopathy.9

SourcesEach quotation was checked word for word against the passage it opens.
  1. MFN2 is involved in ER–mitochondria interactions despite the fact that its actual function as a tether or spacer is still debated (17–20).Carreras-Sureda A, Pihán P, Hetz C, 2017 · The Unfolded Protein Response: At the Intersection between Endoplasmic… · open at passage 7
  2. The long OPA1 isoform is anchored to the inner membrane, where it promotes IMM fusion. The soluble and short OPA1 isoform, found in the intermembrane space, maintains mitochondrial cristae structure (92).Martínez J, Marmisolle I, Tarallo D, Quijano C, 2020 · Mitochondrial Bioenergetics and Dynamics in Secretion Processes · open at passage 22
  3. DRP1 oligomerizes around mitochondria into a ring-like structure constricting the organelle (96).Martínez J, Marmisolle I, Tarallo D, Quijano C, 2020 · Mitochondrial Bioenergetics and Dynamics in Secretion Processes · open at passage 23
  4. ER-mitochondrial contacts play a role in mitochondrial fission, determining the position of the fission events (100)Martínez J, Marmisolle I, Tarallo D, Quijano C, 2020 · Mitochondrial Bioenergetics and Dynamics in Secretion Processes · open at passage 23
  5. Mitochondrial fusion, instead, is a two-step mechanism with the OMM localized GTPases mitofusin 1 and 2 (Mfn1 and Mfn2) ensuring OMM fusion, and the IMM GTPase OPA1 responsible for IMM fusion.Protasoni M, Zeviani M, 2021 · Mitochondrial Structure and Bioenergetics in Normal and Disease Conditions · open at passage 20
  6. OPA1 has been shown to be upstream and epistatic to MIC60 and to be the sole regulator of cristae width and junction diameter and number [25].Protasoni M, Zeviani M, 2021 · Mitochondrial Structure and Bioenergetics in Normal and Disease Conditions · open at passage 12
  7. Stiff ECM promotes mitochondrial fusion by activation of β1-integrin/kindlin-2 (an integrin-binding protein) signaling (Chen et al., 2021).Urra FA, Fuentes-Retamal S, Palominos C, Rodríguez-Lucart…, 2021 · Extracellular Matrix Signals as Drivers of Mitochondrial Bioenergetics and… · open at passage 14
  8. Mitochondrial division or loss of fusion membrane protein (i.e., mitofusin 2 (Mfn2) or OPA1), can drive the removal of damaged organelles from the mitochondrial network to allow a specific form of autophagy, referred as mitophagy [202].Cioffi F, Giacco A, Goglia F, Silvestri E, 2022 · Bioenergetic Aspects of Mitochondrial Actions of Thyroid Hormones · open at passage 37
  9. the increase of mitochondrial fission and mitochondrial DNA damage in retinal vasculature precede apoptosis of retinal endothelial cells in diabetic retinopathy [176, 177]Iorio R, Petricca S, Mattei V, Delle Monache S, 2024 · Horizontal mitochondrial transfer as a novel bioenergetic tool for mesenchymal… · open at passage 44
Linked ideas
Protasoni and Zeviani tie mitochondrial shape to bioenergetic status. Failing mitochondria appear fragmented, and membrane potential is a usual measure of that status.
Cioffi and colleagues report that cristae fold increases under energy pressure to enlarge oxidative phosphorylation areas, under the control of OPA1 and other regulators.
Urra and colleagues link ROS-dependent mitochondrial damage to inflammasome activation, and report that fission affects that activation.
Mitochondrial shape and metabolism change together with cell state, as in migrating cancer cells that adjust metabolism to the stiffness of their surroundings.
Mitophagy and the balance of fusion and fission are described by Cioffi and colleagues as a quality control system that maintains a healthy mitochondrial network.
Urra and colleagues describe how extracellular matrix stiffness shifts mitochondrial fission and fusion in migrating cancer cells.
Mitochondrial quality control and dynamics are part of the setting in which mtDNA mutation and dysfunction are discussed.
Where it is discussedPassages matching mitochondrial fission, mitochondrial fusion, DRP1, mitofusin
2020Mitochondrial Bioenergetics and Dynamics in Secretion Processes · Martínez J, Marmisolle I, Tarallo D…11
2021Extracellular Matrix Signals as Drivers of Mitochondrial Bioenergetics and… · Urra FA, Fuentes-Retamal S, Palominos…4
2021Mitochondrial Structure and Bioenergetics in Normal and Disease Conditions · Protasoni M, Zeviani M4
2024Horizontal mitochondrial transfer as a novel bioenergetic tool for mesenchymal… · Iorio R, Petricca S, Mattei V, Delle…2
2022Bioenergetic Aspects of Mitochondrial Actions of Thyroid Hormones · Cioffi F, Giacco A, Goglia F, Silvestri…2
2017The Unfolded Protein Response: At the Intersection between Endoplasmic… · Carreras-Sureda A, Pihán P, Hetz C1