Carmen A. Mannella, PhD

• Canisius College, BS, Physics, 1969
• University of Pennsylvania, PhD, Biophysics, 1974
• Roswell Park Cancer Institute, PHS/NCI Research Fellow, Biophysics, 1974-76
• Louis University School of Medicine, Postdoctoral Study, Molecular Biology, 1976-78
• Distinguished Alumni Award, Canisius College, Buffalo, NY 2000

Dr. Mannella, PhD is a leading expert in the structure of mitochondria, the cell’s powerhouses.  His special interest is on understanding how the permeability and topology of mitochondrial membranes impact cell bioenergetics. Spurred by this biological interest, Dr. Mannella became involved in development of tools for advancing biological electron microscopy. He led the group that first applied electron tomography to the study of mammalian cells and of microbes, including environmentally important marine organisms (cyanobacteria) and disease-causing parasites, viruses and bacteria.  He also led development in the use of focused ion beams to thin cryogenic biological specimens, a technique now widely used for cryo-electron tomography.

Dr. Mannella’s primary biological research interest continues to be the mitochondrion.  His early research focused on the gated channel, VDAC, the main conduit for ions and metabolites in the mitochondrial outer membrane. He discovered that VDAC forms crystalline arrays in the outer membrane of fungal mitochondria, and used cryo-electron microscopy (along with other biophysical tools such as light spectroscopy and electrophysiology) to define the shape of the pore lumen and conformational changes related to the gating mechanism.

His application of electron tomography to whole mitochondria (isolated and in tissue) revealed the complexity of the organelle’s internal micro-compartments (called cristae) and their interconnectivity via narrow junctions, a discovery that led to revision of canonical textbook models for mitochondria. Other discoveries included the presence of protein “tethers” between the mitochondrial outer membrane and endoplasmic reticulum, implicated in numerous signaling and transport processes.  (There is now molecular evidence for the tethering of mitochondria not only to endoplasmic reticulum but also to other cell components such as peroxisomes, nuclei and lipid droplets.)  Dr. Mannella and his collaborators defined alterations in mitochondrial inner membrane morphology associated with different physiological and pathological states, and with mutations in specific proteins later determined to be involved in crista generation (such as mitofilin and Mgm1/Opa1).  These findings have stimulated an entire field of study (experimental and computational) of the impact of internal diffusion (of protons, metabolites, soluble proteins) and of inner-membrane remodeling on mitochondrial activities.  Dr. Mannella is extending his research in “structural bioenergetics” to heart muscle at the University of Maryland, in conjunction with the laboratory of Dr. Jonathan Lederer.

Electron microscopy, electron tomography, mitochondria, cristae, bioenergetics, membrane remodeling, ion channels, VDAC

N Afzal, WJ Lederer, MS Jafri, CA Mannella (2021) Effect of crista morphology on mitochondrial ATP output: A computational study. Cur Res Physiol 4, 163-176 DOI:10.1016/j.crphys.2021.03.005

CA Mannella, WJ Lederer, MS Jafri (2013) The connection between inner membrane topology and mitochondrial function. J Molec Cell Cardiol 62, 51-57. PMCID: PMC4219563

M Marko, C. Hsieh, R Schalek, J Frank, C Mannella (2007) Focused-ion-beam thinning of frozen-hydrated biological specimens for cryo-electron microscopy [over 300 citations]. Nature Meth 4, 215-217.  PMID: 17277781

CA Mannella (2006) Structure and dynamics of mitochondrial inner membrane cristae [over 400 citations]. Biochim Biophys Acta 1763, 542-548.  PMID: 16730811

G Csordás, C Renken, P Várnai, L Walter, D Weaver, KF Buttle, T Balla, CA Mannella, G Hajnóczky (2006) Structural and functional features and significance of the physical linkage between ER and mitochondria [with cover, over 1100 citations]. J Cell Biol 174, 915-921. PMCID: PMC2064383

L Scorrano, M Ashiya, K Buttle, S Weiler, CA Mannella, SJ Korsmeyer (2002) Distinct pathways remodel mitochondrial cristae for release cytochrome c during apoptosis [over 1100 citations]. Devel Cell 2, 55-67.  PMID: 11782314

T Frey, CA Mannella (2000). The internal structure of mitochondria [with cover, over 900 citations] Trends Biochem Sci 25, 319-324.  PMID: 10871882

XW Guo, PR Smith, B Cognon, D D'Arcangelis, E Dolginova,  CA Mannella (1995) Molecular design of the voltage-dependent, anion-selective channel in the mitochondrial outer membrane [over 100 citations]. J Struct Biol 114, 41-59.  PMID: 7772417