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Open Access Publications from the University of California

Scholarly Works (7 results)

  • Thesis
  • Peer Reviewed
UC Berkeley Electronic Theses and Dissertations (2019)

The increasing efficiency and adoption rate of light-emitting diodes (LEDs) for lighting is forecasted to lead to large energy savings in that sector. Intrinsic self-refrigeration, which surprisingly accompanies the emission of light from an LED, might allow the same technology to be harnessed for new applications. In the first half of this dissertation, I will discuss whether refrigeration and cooling, which also account for a large share of world energy consumption, comprise a realistic future energy application for optoelectronics. To date, electroluminescent cooling has eluded direct observation at practical power densities, since a pre-requisite for net cooling is the near-complete elimination of LED internal losses that dissipate heat. I will propose a near-ideal-efficiency LED structure, realizable with existing optoelectronic material quality and device processing capabilities, to predict the technological limits of electroluminescent refrigeration. I will show that LED-based cooling can realistically be more efficient than solid-state alternatives like thermoelectric cooling, particularly for cryogenic applications and at moderate power densities.

In the second half of this dissertation, I will discuss a new hardware accelerator for difficult combinatorial optimization problems. These problems are abundant in modern society, in the fields of operations research, artificial intelligence, chip design, financial optimization, medicine, and many others. They are difficult in that no algorithm has yet been found that solves them efficiently, but the increasing computational power of digital computers has allowed these problems to be routinely tackled. As conventional computers reach their scaling limits, however, alternative hardware architectures are being explored to accelerate computationally intensive tasks like machine learning and combinatorial optimization. Here, I will discuss the design of a new optimization machine, implemented using a network of coupled analog electrical oscillators. The machine uses an unconventional search mechanism to discover the global minimum of the Ising problem, a difficult problem that maps quickly onto other hard optimization problems. I will present the simulated performance of this machine for moderately sized problems with all-to-all connectivity and discuss its potential to scale to larger problems.

    Cover page: Optoelectronics for refrigeration and analog circuits for combinatorial optimization
    • Article
    • Peer Reviewed
    UC Berkeley Previously Published Works (2021)
    Deficiencies in mitochondrial import cause the toxic accumulation of non-imported mitochondrial precursor proteins. Numerous fates for non-imported mitochondrial precursors have been identified in budding yeast, including proteasomal destruction, deposition into protein aggregates, and mistargeting to other organelles. Amongst organelles, the ER has emerged as a key destination for a subset of non-imported mitochondrial proteins. However, how ER targeting of various types of mitochondrial proteins is achieved remains incompletely understood. Here, we show that the ER delivery of endogenous mitochondrial transmembrane proteins, especially those belonging to the SLC25A mitochondrial carrier family, is dependent on the guided entry of tail-anchored proteins (GET) complex. Without a functional GET pathway, non-imported mitochondrial proteins destined for the ER are alternatively sequestered into Hsp42-dependent protein foci. Loss of the GET pathway is detrimental to yeast cells experiencing mitochondrial import failure and prevents re-import of mitochondrial proteins from the ER via the ER-SURF pathway. Overall, this study outlines an important role for the GET complex in ER targeting of non-imported mitochondrial carrier proteins.
      Cover page: ER targeting of non-imported mitochondrial carrier proteins is dependent on the GET pathway.
      • Article
      • Peer Reviewed
      UC Berkeley Previously Published Works (2020)
      Optimization is a major part of human effort. While being mathematical, optimization is also built into physics. For example, physics has the Principle of Least Action; the Principle of Minimum Power Dissipation, also called Minimum Entropy Generation; and the Variational Principle. Physics also has Physical Annealing, which, of course, preceded computational Simulated Annealing. Physics has the Adiabatic Principle, which, in its quantum form, is called Quantum Annealing. Thus, physical machines can solve the mathematical problem of optimization, including constraints. Binary constraints can be built into the physical optimization. In that case, the machines are digital in the same sense that a flip-flop is digital. A wide variety of machines have had recent success at optimizing the Ising magnetic energy. We demonstrate in this paper that almost all those machines perform optimization according to the Principle of Minimum Power Dissipation as put forth by Onsager. Further, we show that this optimization is in fact equivalent to Lagrange multiplier optimization for constrained problems. We find that the physical gain coefficients that drive those systems actually play the role of the corresponding Lagrange multipliers.
        Cover page: Physics successfully implements Lagrange multiplier optimization
        • Article
        • Peer Reviewed
        UC Berkeley Previously Published Works (2020)
        Mitochondria are dynamic organelles with essential roles in signaling and metabolism. We recently identified a cellular structure called the mitochondrial-derived compartment (MDC) that is generated from mitochondria in response to amino acid overabundance stress. How cells form MDCs is unclear. Here, we show that MDCs are dynamic structures that form and stably persist at sites of contact between the ER and mitochondria. MDC biogenesis requires the ER-mitochondria encounter structure (ERMES) and the conserved GTPase Gem1, factors previously implicated in lipid exchange and membrane tethering at ER-mitochondria contacts. Interestingly, common genetic suppressors of abnormalities displayed by ERMES mutants exhibit distinct abilities to rescue MDC formation in ERMES-depleted strains and are incapable of rescuing MDC formation in cells lacking Gem1. Thus, the function of ERMES and Gem1 in MDC biogenesis may extend beyond their conventional role in maintaining mitochondrial phospholipid homeostasis. Overall, this study identifies an important function for ER-mitochondria contacts in the biogenesis of MDCs.
          Cover page: ER-mitochondria contacts promote mitochondrial-derived compartment biogenesis.
          • Article
          • Peer Reviewed
          UC Berkeley Previously Published Works (2021)
          Mitochondrial import deficiency causes cellular toxicity due to the accumulation of non-imported mitochondrial precursor proteins, termed mitoprotein-induced stress. Despite the burden mis-localized mitochondrial precursors place on cells, our understanding of the systems that dispose of these proteins is incomplete. Here, we cataloged the location and steady-state abundance of mitochondrial precursor proteins during mitochondrial impairment in Saccharomyces cerevisiae. We found that a number of non-imported mitochondrial proteins localize to the nucleus, where they are subjected to proteasome-dependent degradation through a process we term nuclear-associated mitoprotein degradation (mitoNUC). Recognition and destruction of mitochondrial precursors by the mitoNUC pathway requires the presence of an N-terminal mitochondrial targeting sequence and is mediated by combined action of the E3 ubiquitin ligases San1, Ubr1, and Doa10. Impaired breakdown of precursors leads to alternative sequestration in nuclear-associated foci. These results identify the nucleus as an important destination for the disposal of non-imported mitochondrial precursors.
            Cover page: A nuclear-based quality control pathway for non-imported mitochondrial proteins.
            • Article
            • Peer Reviewed
            UC Berkeley Previously Published Works (2024)
            Cells utilize multiple mechanisms to maintain mitochondrial homeostasis. We recently characterized a pathway that remodels mitochondria in response to metabolic alterations and protein overload stress. This remodeling occurs via the formation of large membranous structures from the mitochondrial outer membrane called mitochondrial-derived compartments (MDCs), which are eventually released from mitochondria and degraded. Here, we conducted a microscopy-based screen in budding yeast to identify factors that regulate MDC formation. We found that two phospholipids, cardiolipin (CL) and phosphatidylethanolamine (PE), differentially regulate MDC biogenesis. CL depletion impairs MDC biogenesis, whereas blocking mitochondrial PE production leads to constitutive MDC formation. Additionally, in response to metabolic MDC activators, cellular and mitochondrial PE declines, and overexpressing mitochondrial PE synthesis enzymes suppress MDC biogenesis. Altogether, our data indicate a requirement for CL in MDC biogenesis and suggest that PE depletion may stimulate MDC formation downstream of MDC-inducing metabolic stress.
              Cover page: The phospholipids cardiolipin and phosphatidylethanolamine differentially regulate MDC biogenesis.
              • Article
              • Peer Reviewed
              UC Berkeley Previously Published Works (2021)
              Amino acids are essential building blocks of life. However, increasing evidence suggests that elevated amino acids cause cellular toxicity associated with numerous metabolic disorders. How cells cope with elevated amino acids remains poorly understood. Here, we show that a previously identified cellular structure, the mitochondrial-derived compartment (MDC), functions to protect cells from amino acid stress. In response to amino acid elevation, MDCs are generated from mitochondria, where they selectively sequester and deplete SLC25A nutrient carriers and their associated import receptor Tom70 from the organelle. Generation of MDCs promotes amino acid catabolism, and their formation occurs simultaneously with transporter removal at the plasma membrane via the multivesicular body (MVB) pathway. The combined loss of vacuolar amino acid storage, MVBs, and MDCs renders cells sensitive to high amino acid stress. Thus, we propose that MDCs operate as part of a coordinated cell network that facilitates amino acid homeostasis through post-translational nutrient transporter remodeling.
                Cover page: Mitochondrial-derived compartments facilitate cellular adaptation to amino acid stressCreative Commons 'BY' version 4.0 license
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