Table 1.
List of mitochondrial-shaping proteins.
| Gene Name (with Synonyms) | Protein Name | Function | Localization | Shaping Function | References |
|---|---|---|---|---|---|
| APOO, FAM121B, MIC23, MIC26, My025, UNQ1866/PRO4302 | MICOS Complex subunit MIC26 (Apolipoprotein O) (MICOS Complex subunit MIC23) (Protein FAM121B) | Component of the MICOS Complex, a large protein Complex of the inner mitochondrial membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane | IMM | Cristae shape | [14,15,16] |
| APOOL, CXorf33, FAM121A, MIC27, UNQ8193/PRO23204 | MICOS Complex subunit MIC27 (Apolipoprotein O-like) (Protein FAM121A) | Component of the MICOS Complex, a large protein Complex of the inner mitochondrial membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane | IMM | Cristae shape | [14,15,17,18] |
| ATP5A1, ATP5B, ATP5C1, ATP5D, ATP5E, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5H, ATP5I, ATP5J, ATP5J2, ATP5L, ATP5O, MT-ATP6, MT-ATP8 | ATP synthase | ATP production | IMM | Cristae shape | [3,15,19] |
| ATPIF1, ATPI | ATPase inhibitor, mitochondrial (Inhibitor of F(1)F(o)-ATPase) (IF(1)) (IF1) | ATP production regulation | Matrix | Cristae shape | [3,20] |
| BAK1, BAK, BCL2L7, CDN1 | Bcl-2 homologous antagonist/killer (Apoptosis regulator BAK) | Promotes apoptosis | OMM | OMM permeabilization | [3,21] |
| BAX, BCL2L4 | Apoptosis regulator BAX | Accelerates apoptosis | OMM | OMM permeabilization | [3,19,21,22] |
| BCL2 | Apoptosis regulator Bcl-2 | Promotes cell survival | OMM | OMM permeabilization | [3,22] |
| BCL2A1, BCL2L5, BFL1, GRS, HBPA1 | Bcl-2-related protein A1 (A1-A) (Hemopoietic-specific early response protein) (Protein BFL-1) | Promotes cell survival | OMM | Not clear function | [23,24] |
| BCL2L11, BIM | Bcl-2-like protein 11 (Bcl2-L-11) (Bcl2-interacting mediator of cell death) | Induces apoptosis and anoikis | IMM | Cristae remodeling | [25,26] |
| BID | BH3-interacting domain death agonist | The major proteolytic product p15 BID allows the release of cytochrome c | IMM | Cristae remodeling | [25,27] |
| BIK, NBK | Bcl-2-interacting killer (Apoptosis inducer NBK) (BIP1) (BP4) | Promotes apoptosis | IMM | Cristae remodeling | [25,28] |
| CHCHD3, MIC19, MINOS3 | MICOS Complex subunit MIC19 (Coiled-coil-helix-coiled-coil-helix domain-containing protein 3) | Component of the MICOS Complex, a large protein Complex of the inner mitochondrial membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane | IMM | Cristae shape | [14,16,18] |
| COA3, CCDC56, MITRAC12, HSPC009 | Cytochrome c oxidase assembly factor 3 homolog, mitochondrial (Coiled-coil domain-containing protein 56) (Mitochondrial translation regulation assembly intermediate of cytochrome c oxidase protein of 12 kDa) | Core component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase) Complex, which regulates cytochrome c oxidase assembly. | IMM | Cytochrome c oxidase | [29,30] |
| COX4I1, COX4I2, COX5A, COX5B, COX6A1, COX6A2, COX6B1, COX6B2, COX6C, COX7A1, COX7A2, COX7B, COX7B2, COX7C, COX8A, COX8C, MT-CO1, MT-CO2, MT-CO3 | Mitochondrial Complex IV: cytochrome c oxidase subunits | ATP production | IMM | Cristae shape | [18] |
| CYC1, MT-CYB, UQCR10, UQCR11, UQCRB, UQCRC1, UQCRC2, UQCRFS1, UQCRH, UQCRQ | Mitochondrial Complex III: ubiquinol-cytochrome c reductase Complex subunits (UQCR) | ATP production | IMM | Cristae shape | [18] |
| DNAJC19, TIM14, TIMM14 | Mitochondrial import inner membrane translocase subunit TIM14 (DnaJ homolog subfamily C member 19) | Probable component of the PAM Complex, a Complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner | IMM | Crista shape | [15,31,32] |
| DNM1L, DLP1, DRP1 | Dynamin-1-like protein (EC 3.6.5.5) (Dnm1p/Vps1p-like protein) (DVLP) (Dynamin family member proline-rich carboxyl-terminal domain less) (Dymple) (Dynamin-like protein) (Dynamin-like protein 4) (Dynamin-like protein IV) (HdynIV) (Dynamin-related protein 1) | Mitochondrial and peroxisome division | OMM and cytosol | Fission | [3,18,22] |
| DNM2, DYN2 | Dynamin-2 (EC 3.6.5.5) | Microtubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP | Cytosol | Fission | [4,33] |
| FIS1, TTC11, CGI-135 | Mitochondrial fission 1 protein (FIS1 homolog) (hFis1) (Tetratricopeptide repeat protein 11) (TPR repeat protein 11) | Mitochondrial fragmentation | OMM | Fission | [3,19,22] |
| FUNDC1 | FUN14 domain-containing protein 1FUN14 domain-containing protein 1 | Mitophagy | OMM | Fission | [29,34,35,36] |
| GDAP1 | Ganglioside-induced differentiation-associated protein 1 | Mitochondrial fission | OMM | Fission | [1,19,22] |
| hfzo1 | Mitochondrial transmembrane GTPase Fzo-1 | FUNDC1 mediates highly selective mitochondrial clearance under hypoxic conditions without impacting general autophagy | OMM | Fusion | [19] |
| IMMT, HMP, MIC60, MINOS2, PIG4, PIG52 | MICOS Complex subunit MIC60(Cell proliferation-inducing gene 4/52 protein) (Inner mitochondrial membrane protein) (Mitofilin) (p87/89) | Component of the MICOS Complex, a large protein Complex of the inner mitochondrial membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane | IMM | Cristae shape | [15,16,18,19,37] |
| INF2, C14orf151, C14orf173 | Inverted formin-2 (HBEBP2-binding protein C) | Severs actin filaments and accelerates their polymerization and depolymerization | Cytosol | Mitochondrial constriction | [29,38] |
| LETM1 | Mitochondrial proton/calcium exchanger protein (Leucine zipper-EF-hand-containing transmembrane protein 1) | Mitochondrial proton/calcium antiporter that mediates proton-dependent calcium efflux from mitochondria | IMM | Fission | [1,22,39] |
| MARCH5, RNF153 | E3 ubiquitin-protein ligase MARCH5 (EC 2.3.2.27) (Membrane-associated RING finger protein 5) (Membrane-associated RING-CH protein V) (MARCH-V) (Mitochondrial ubiquitin ligase) (MITOL) (RING finger protein 153) (RING-type E3 ubiquitin transferase MARCH5) | Membrane-bound E3 ligase for mitochondrial morphology control | OMM | Fission | [1,19] |
| MAVS, IPS1, KIAA1271, VISA | Mitochondrial antiviral-signaling protein (MAVS) (CARD adapter inducing interferon beta) (Cardif) (Interferon beta promoter stimulator protein 1) (IPS-1) (Putative NF-kappa-B-activating protein 031N) (Virus-induced-signaling adapter) (VISA) | Required for innate immune response against viruses | OMM | Fusion | [22,40] |
| MCL1, BCL2L3 | Induced myeloid leukemia cell differentiation protein Mcl-1 (Bcl-2-like protein 3) (Bcl2-L-3) (Bcl-2-related protein EAT/mcl1) (mcl1/EAT) | Regulation of apoptosis | IMM and OMM | Cristae shape (IMM isoform) | [18,29,41,42] |
| MFF, C2orf33, AD030, AD033, GL004 | Mitochondrial Fission Factor | Mitochondrial and peroxisome division | OMM | Fission | [3,19] |
| MFN1 | Mitofusin-1 (EC 3.6.5.-) (Fzo homolog) (Transmembrane GTPase MFN1) | Mitochondrial fusion | OMM | Fusion | [18,22,43] |
| MFN2, CPRP1, KIAA0214 | Mitofusin-2 (EC 3.6.5.-) (Transmembrane GTPase MFN2) | Regulates mitochondrial clustering and fusion | OMM | Fusion | [18,22,43] |
| MIC13, C19orf70, QIL1 | MICOS Complex subunit MIC13 (Protein P117) | Component of the MICOS Complex, a large protein Complex of the inner mitochondrial membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane | IMM | Cristae shape | [15,18] |
| MIEF1, MID51, SMCR7L | Mid51/Mief, mitochondrial dynamics proteins of 51 | Component of the MICOS Complex, a large protein Complex of the inner mitochondrial membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane | OMM | Fission | [3,19] |
| MIEF2, MID49, SMCR7 | Mitochondrial dynamics protein MID49 (Mitochondrial dynamics protein of 49 kDa) (Mitochondrial elongation factor 2) (Smith-Magenis syndrome chromosomal region candidate gene 7 protein) | Component of the MICOS Complex, a large protein Complex of the inner mitochondrial membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane | OMM | Fission | [3,19] |
| MIGA1, FAM73A | Mitoguardin 1 (Protein FAM73A) | Regulator of mitochondrial fusion | OMM | Fusion | [4,44] |
| MIGA2, C9orf54, FAM73B, PSEC0112 | Mitoguardin 2 (Protein FAM73B) | Regulator of mitochondrial fusion | OMM | Fusion | [4,44] |
| MINOS1, C1orf151, MIC10 | MICOS Complex subunit MIC10 (Inner mitochondrial membrane organizing system protein 1) | Maintenance of cristae junctions, inner membrane architecture, and formation of contact sites to the outer membrane | IMM | Cristae shape | [15,18] |
| MTFP1, MTP18, HSPC242, My022 | Mitochondrial fission process protein 1(Mitochondrial 18 kDa protein) (MTP18) | Involved in the mitochondrial division probably by regulating membrane fission | IMM | Fission | [1,22,45] |
| MUL1, C1orf166, GIDE, MAPL, MULAN, RNF218 | Mitochondrial ubiquitin ligase activator of NFKB 1 (EC 2.3.2.27) (E3 SUMO-protein ligase MUL1) (E3 ubiquitin-protein ligase MUL1) (Growth inhibition and death E3 ligase) (Mitochondrial-anchored protein ligase) (MAPL) (Putative NF-kappa-B-activating protein 266) (RING finger protein 218) (RING-type E3 ubiquitin transferase NFKB 1) | Ubiquitin ligase activity | OMM | Fusion | [19,29] |
| NFE2L2, NRF2 | Nuclear factor erythroid 2-related factor 2 (NF-E2-related factor 2) (NFE2-related factor 2) (HEBP1) (Nuclear factor, erythroid derived 2, like 2) | Transcription activator that binds to antioxidant response (ARE) elements in the promoter regions of target genes | Cytosol | Fusion | [29,46,47] |
| NRF1 | Nuclear respiratory factor 1 (NRF-1) (Alpha palindromic-binding protein) (Alpha-pal) | Transcription factor implicated in the control of nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication | Cytosol | Fission | [29,46,48,49] |
| OMA1, MPRP1 | Metalloendopeptidase OMA1, mitochondrial (EC 3.4.24.-) (Metalloprotease-related protein 1) (MPRP-1) (Overlapping with the m-AAA protease 1 homolog) | Metalloprotease that is part of the quality control system in the inner membrane of mitochondria | IMM | Fusion | [1,19] |
| OPA1, KIAA0567 | Dynamin-like 120 kDa protein, mitochondrial (EC 3.6.5.5) (Optic atrophy protein 1) (Cleaved into: Dynamin-like 120 kDa protein, form S1) | Opa1 mediates dynamics changes in cristae morphology that correlate with the metabolic state of the organelle | IMM | Cristae shape, fusion | [1,3,15,18,22,50] |
| PARL, PSARL, PRO2207 | Presenilins-associated rhomboid-like protein, mitochondrial (EC 3.4.21.105) (Mitochondrial intramembrane cleaving protease PARL) (Cleaved into: P-beta (Pbeta)) | Required for the control of apoptosis | IMM | Mitochondrial morphology | [1,51] |
| PGAM5 | Serine/threonine-protein phosphatase PGAM5, mitochondrial (EC 3.1.3.16) (Bcl-XL-binding protein v68) (Phosphoglycerate mutase family member 5) | Displays phosphatase activity for serine/threonine residues, as well as dephosphorylates and activates MAP3K5 kinase | OMM | Fission | [1,29,52] |
| PHB | Prohibitin | Prohibitin inhibits DNA synthesis; it has a role in regulating proliferation | IMM | Cristae shape | [1,15,18,31,53] |
| PHB2, BAP, REA | Prohibitin-2 (B-cell receptor-associated protein BAP37) (D-prohibitin) (Repressor of estrogen receptor activity) | Acts as a mediator of transcriptional repression by nuclear hormone receptors via the recruitment of histone deacetylases (by similarity); functions as an estrogen receptor (ER)-selective coregulator that potentiates the inhibitory activities of antiestrogens and represses the activity of estrogens | IMM | Cristae shape | [1,15,18] |
| PINK1 | Serine/threonine-protein kinase PINK1, mitochondrial (EC 2.7.11.1) (BRPK) (PTEN-induced putative kinase protein 1) | Protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins | OMM | Fission | [1,54] |
| PLD6 | Mitochondrial cardiolipin hydrolase (EC 3.1.-.-) (Choline phosphatase 6) (Mitochondrial phospholipase) (MitoPLD) (Phosphatidylcholine-hydrolyzing phospholipase D6) (Phospholipase D6) (PLD 6) (Protein zucchini homolog) | Proposed to act as a cardiolipin hydrolase to generate phosphatidic acid at the mitochondrial surface | OMM | Fusion | [4,19,22,45] |
| PPARGC1A, LEM6, PGC1, PGC1A, PPARGC1 | Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1-alpha) (PPAR-gamma coactivator 1-alpha) (PPARGC-1-alpha) (Ligand effect modulator 6) | Transcriptional coactivator for steroid receptors and nuclear receptors | Cytoplasm and nucleus | Fusion | [29,49,55] |
| PPARGC1B, PERC, PGC1, PGC1B, PPARGC1 | Peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC-1-beta) (PPAR-gamma coactivator 1-beta) (PPARGC-1-beta) (PGC-1-related estrogen receptor alpha coactivator) | Plays the role of stimulator of transcription factors and nuclear receptors activities | Nucleus | Fusion | [29,55,56] |
| PRELID1, PRELI, CGI-106, SBBI12 | PRELI domain-containing protein 1, mitochondrial (25 kDa protein of relevant evolutionary and lymphoid interest) (Px19-like protein) | Involved in the modulation of the mitochondrial apoptotic pathway by ensuring the accumulation of cardiolipin (CL) in mitochondrial membranes | Intermembrane space | Fission | [57,58] |
| PRKN, PARK2 | E3 ubiquitin-protein ligase parkin (Parkin) (EC 2.3.2.-) (Parkin RBR E3 ubiquitin-protein ligase) (Parkinson juvenile disease protein 2) (Parkinson disease protein 2) | Functions within a multiprotein E3 ubiquitin ligase Complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins | Cytosol and mitochondria | Fission | [1,54,59,60] |
| ROMO1, C20orf52 | Reactive oxygen species modulator 1(ROS modulator 1) (Epididymis tissue protein Li 175) (Glyrichin) (Mitochondrial targeting GxxxG motif protein) (MTGM) (Protein MGR2 homolog) | Induces the production of reactive oxygen species (ROS), which are necessary for cell proliferation | IMM | Fusion | [29,61] |
| SAMM50, SAM50, CGI-51, TRG3 | Sorting and assembly machinery component 50 homolog (Transformation-related gene 3 protein) (TRG-3) | Plays a crucial role in the maintenance of the structure of mitochondrial cristae and the proper assembly of the mitochondrial respiratory chain Complexes | OMM | Cristae shape | [18] |
| SH3GLB1, KIAA0491, CGI-61 | Endophilin-B1 (Bax-interacting factor 1) (Bif-1) (SH3 domain-containing GRB2-like protein B1) | Outer mitochondrial dynamics | OMM | OMM permeability | [1,22,62] |
| SH3GLB2, KIAA1848, PP578 | Endophilin-B2 (SH3 domain-containing GRB2-like protein B2) | Mitophagy | Cytosol | Fission | [63] |
| SLC25A10, DIC | Mitochondrial dicarboxylate carrier (Solute carrier family 25 member 10) | Involved in the translocation of malonate, malate, and succinate in exchange for phosphate, sulfate, sulfite, or thiosulfate across the inner mitochondrial membrane | IMM | Cristae shape | [18,50] |
| SLC25A11, SLC20A4 | Mitochondrial 2-oxoglutarate/malate carrier protein (OGCP) (Solute carrier family 25 member 11) | Catalyzes the transport of 2-oxoglutarate across the inner mitochondrial membrane in an electroneutral exchange for malate or other dicarboxylic acids, and plays an important role in several metabolic processes, including the malate-aspartate shuttle, the oxoglutarate/isocitrate shuttle, in gluconeogenesis from lactate, and in nitrogen metabolism | IMM | Cristae shape | [18,50] |
| SLC25A12, ARALAR1 | Calcium-binding mitochondrial carrier protein Aralar1 (Mitochondrial aspartate glutamate carrier 1) (Solute carrier family 25 member 12) | Catalyzes the calcium-dependent exchange of cytoplasmic glutamate with mitochondrial aspartate across the inner mitochondrial membrane; may have a function in the urea cycle | IMM | Cristae shape | [18,50] |
| SLC25A13, ARALAR2 | Calcium-binding mitochondrial carrier protein Aralar2 (Citrin) (Mitochondrial aspartate glutamate carrier 2) (Solute carrier family 25 member 13) | Catalyzes the calcium-dependent exchange of cytoplasmic glutamate with mitochondrial aspartate across the inner mitochondrial membrane; may have a function in the urea cycle | IMM | Cristae shape | [18,50] |
| SLC25A38 | Solute carrier family 25 member 38, Appoptosin | Mitochondrial import machinery | IMM | Fusion | [29,64] |
| SMAD2, MADH2, MADR2 | Mothers against decapentaplegic homolog 2 (MAD homolog 2) (Mothers against DPP homolog 2) (JV18-1) (Mad-related protein 2) (hMAD-2) (SMAD family member 2) (SMAD 2) (Smad2) (hSMAD2) | Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases | Cytosol | Fusion | [29,65] |
| SPG7, CAR, CMAR, PGN | Paraplegin (EC 3.4.24.-) (Cell matrix adhesion regulator) (Spastic paraplegia 7 protein) | ATP-dependent zinc metalloprotease | IMM | Cristae shape | [18] |
| SPG7, CAR, CMAR, PGN | Paraplegin (EC 3.4.24.-) (Cell matrix adhesion regulator) (Spastic paraplegia 7 protein) | ATP-dependent zinc metalloprotease | IMM | Fusion | [1,22,51] |
| STOML2, SLP2, HSPC108 | Stomatin-like protein 2, mitochondrial(SLP-2) (EPB72-like protein 2) (Paraprotein target 7) (Paratarg-7) | Mitochondrial protein that probably regulates the biogenesis and the activity of mitochondria; stimulates cardiolipin biosynthesis, binds cardiolipin-enriched membranes where it recruits and stabilizes some proteins including prohibitin, and may therefore act in the organization of functional microdomains in mitochondrial membranes | IMM | Cristae shape/Stabilize IM structure | [15,18] |
| SYNJ2, KIAA0348 | Synaptojanin-2(EC 3.1.3.36) (Synaptic inositol 1,4,5-trisphosphate 5-phosphatase 2) | Membrane trafficking and signaling transduction | Cytosol | Mitochondrial aggregation | [66] |
| TAZ, EFE2, G4.5 | Tafazzin (Protein G4.5) | Some isoforms may be involved in cardiolipin (CL) metabolism | OMM | Cristae shape | [15,16,67,68] |
| TFAM, TCF6, TCF6L2 | Transcription factor A, mitochondrial (mtTFA) (Mitochondrial transcription factor 1) (MtTF1) (Transcription factor 6) (TCF-6) (Transcription factor 6-like 2) | Binds to the mitochondrial light strand promoter and functions in mitochondrial transcription regulation | Matrix | Mitochondrial biogenesis | [29,46] |
| TRAK1, KIAA1042, OIP106 | Trafficking kinesin-binding protein 1 (106 kDa O-GlcNAc transferase-interacting protein) | Organelle trafficking | OMM and cytosol | Fusion | [1,4,19] |
| TRAK2, ALS2CR3, KIAA0549 | Trafficking kinesin-binding protein 2 (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 3 protein) | Organelle trafficking | OMM and cytosol | Fusion | [1,4,19] |
| UQCC3, C11orf83, UNQ655/PRO1286 | Ubiquinol-cytochrome-c reductase Complex assembly factor 3 | Required for the assembly of the ubiquinol-cytochrome c reductase Complex (mitochondrial respiratory chain Complex III or cytochrome b-c1 Complex), mediating cytochrome b recruitment and probably stabilization within the Complex | IMM | Cristae shape | [18,69] |
| VAT1 | Synaptic vesicle membrane protein VAT-1 homolog (EC 1.-.-.-) (Mitofusin-binding protein) (Protein MIB) | Negatively regulates mitochondrial fusion | OMM | Fusion | [1,19,22,70] |
| YME1L1, FTSH1, YME1L, UNQ1868/PRO4304 | ATP-dependent zinc metalloprotease YME1L1 (EC 3.4.24.-) (ATP-dependent metalloprotease FtsH1) (Meg-4) (Presenilin-associated metalloprotease) (PAMP) (YME1-like protein 1) | Putative ATP-dependent protease; plays a role in mitochondrial organization and mitochondrial protein metabolism, including the degradation of PRELID1 and OPA1 | IMM | Cristae shape | [19,58] |